Search results for: mitochondrial disease

Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

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Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

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Authors: Pratibha Srivastava, Ayyamperumal Jeyaprakash, Gary Steck, Jason Stanley, Leroy Whilby

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Exotic, invasive tephritid fruit flies (Diptera: Tephritidae) are a major threat to fruit and vegetable industries in the United States. The establishment of pest fruit fly in the agricultural industries and produce severe ecological and economic impacts on agricultural diversification and trade. Detection and identification of these agricultural pests in a timely manner will facilitate the possibility of eradication from newly invaded areas. Identification of larval stages to species level is difficult, but is required to determine pest loads and their pathways into the United States. The aim of this study is the New World genus, Anastrepha which includes pests of major economic importance. Mitochondrial cytochrome c oxidase I (COI) gene sequences were amplified from Anastrepha fraterculus specimens collected from South America (Ecuador and Peru). Phylogenetic analysis was performed to characterize the Anastrepha fraterculus complex at a molecular level. During phylogenetics analysis numerous nuclear mitochondrial pseudogenes (numts) were discovered in different specimens. The numts are nonfunctional copies of the mtDNA present in the nucleus and are easily coamplified with the mitochondrial COI gene copy by using conserved universal primers. This is problematic for DNA Barcoding, which attempts to characterize all living organisms by using the COI gene. This study is significant for national quarantine use, as morphological diagnostics to separate larvae of the various members remain poorly developed.

Keywords: tephritid, Anastrepha fraterculus, COI, numts

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Authors: Mateen A. Khan, Elizabeth J. Theil, Dixie J. Goss

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Cellular iron homeostasis is accomplished by the coordinated regulated expression of iron uptake, storage, and export. Iron regulate the translation of ferritin and mitochondrial aconitase iron responsive element (IRE)-mRNA by interaction with an iron regulatory protein (IRPs). Iron increases protein biosynthesis encoded in iron responsive element. The noncoding structure IRE-mRNA, approximately 30-nt, folds into a stem loop to control synthesis of proteins in iron trafficking, cell cycling, and nervous system function. Fluorescence anisotropy measurements showed the presence of one binding site on IRP1 for ferritin and mitochondrial aconitase IRE-mRNA. Scatchard analysis revealed the binding affinity (Kₐ) and average binding sites (n) for ferritin and mitochondrial aconitase IRE-mRNA were 68.7 x 10⁶ M⁻¹ and 9.2 x 10⁶ M⁻¹, respectively. In order to understand the relative importance of equilibrium and stability, we further report the contribution of electrostatic interactions in the overall binding of two IRE-mRNA with IRP1. The fluorescence quenching of IRP1 protein was measured at different ionic strengths. The binding affinity of IRE-mRNA to IRP1 decreases with increasing ionic strength, but the number of binding sites was independent of ionic strength. Such results indicate a differential contribution of electrostatics to the interaction of IRE-mRNA with IRP1, possibly related to helix bending or stem interactions and an overall conformational change. Selective destabilization of ferritin and mitochondrial aconitase RNA/protein complexes as reported here explain in part the quantitative differences in signal response to iron in vivo and indicate possible new regulatory interactions.

Keywords: IRE-mRNA, IRP1, binding, ionic strength

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Authors: Blessing Ojeme, Frederick Quinn, Russell Karls, Shannon Quinn

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The detection and segmentation of mitochondria from fluorescence microscopy are crucial for understanding the complex structure of the nervous system. However, the constant fission and fusion of mitochondria and image distortion in the background make the task of detection and segmentation challenging. In the literature, a number of open-source software tools and artificial intelligence (AI) methods have been described for analyzing mitochondrial images, achieving remarkable classification and quantitation results. However, the availability of combined expertise in the medical field and AI required to utilize these tools poses a challenge to its full adoption and use in clinical settings. Motivated by the advantages of automated methods in terms of good performance, minimum detection time, ease of implementation, and cross-platform compatibility, this study proposes a fully automated framework for the detection and segmentation of mitochondria using both image shape information and descriptive statistics. Using the low-cost, open-source python and openCV library, the algorithms are implemented in three stages: pre-processing, image binarization, and coarse-to-fine segmentation. The proposed model is validated using the mitochondrial fluorescence dataset. Ground truth labels generated using a Lab kit were also used to evaluate the performance of our detection and segmentation model. The study produces good detection and segmentation results and reports the challenges encountered during the image analysis of mitochondrial morphology from the fluorescence mitochondrial dataset. A discussion on the methods and future perspectives of fully automated frameworks conclude the paper.

Keywords: 2D, binarization, CLAHE, detection, fluorescence microscopy, mitochondria, segmentation

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Authors: H. Imad, Y. Cheah, O. Aamera

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The aims of this research are to study the mitochondrial non-coding region by using the Sanger sequencing technique and establish the degree of variation characteristics of a fragment. FTA® Technology (FTA™ paper DNA extraction) utilized to extract DNA. A portion of a non-coding region encompassing positions 37 to 340 amplified in accordance with the Anderson reference sequence. PCR products purified by EZ-10 spin column then sequenced and detected by using the ABI 3730xL DNA Analyzer. New polymorphic positions 57, 63, and 101 are described may in future be suitable sources for identification purpose. The data obtained can be used to identify variable nucleotide positions characterized by frequent occurrence most promising for identification variants.

Keywords: encompassing nucleotide positions 37 to 340, HVII, Iraq, mitochondrial DNA, polymorphism, frequency

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Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Marek Halenár, Eva Tvrdá, Tomáš Slanina, Ľubomír Ondruška, Eduard Kolesár, Peter Massányi, Adriana Kolesárová

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The present in vitro study was designed to reveal whether amygdalin (AMG) is able to cause changes to the motility, viability and mitochondrial activity of rabbit spermatozoa. New Zealand White rabbits (n = 10) aged four months were used in the study. Semen samples were collected from each animal and used for the in vitro incubation. The samples were divided into five equal parts and diluted with saline supplemented with 0, 0.5, 1, 2.5 and 5 mg/mL AMG. At times 0h, 3h and 5h spermatozoa motion parameters were assessed using the SpermVision™ computer-aided sperm analysis (CASA) system, cell viability was examined with the metabolic activity (MTT) assay, and the eosin-nigrosin staining technique was used to evaluate the viability of rabbit spermatozoa. All AMG concentrations exhibited stimulating effects on the spermatozoa activity, as shown by a significant preservation of the motility (P<0.05 with respect to 0.5 mg/mL and 1 mg/mL AMG; Time 5 h) and mitochondrial activity (P< 0.05 in case of 0.5 mg/mL AMG; P< 0.01 in case of 1 mg/mL AMG; P < 0.001 with respect to 2.5 mg/mL and 5 mg/mL AMG; Time 5 h). None of the AMG doses supplemented had any significant impact of the spermatozoa viability. In conclusion, the data revealed that short-term co-incubation of spermatozoa with AMG may result in a higher preservation of the sperm structural integrity and functional activity.

Keywords: amygdalin, CASA, mitochondrial activity, motility, rabbits, spermatozoa, viability

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Authors: Nafisa Komilova, Plamena Angelova, Andrey Abramov, Ulugbek Mirkhodjaev

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is induced by the loss of dopaminergic neurons in the midbrain. The mechanism of neurodegeneration is associated with the aggregation of misfolded proteins, oxidative stress, and mitochondrial disfunction. Considering this, the process of removal of unwanted organelles or proteins by autophagy is vitally important in neurons, and activation of these processes could be protective in PD. Short-time acidification of cytosol can activate mitophagy and autophagy, and here we used sodium pyruvate and sodium lactate in human fibroblasts with PD mutations (Pink1, Pink1/Park2, α-syn triplication, A53T) to induce changes in intracellular pH. We have found that both lactate and pyruvate in millimolar concentrations can induce short-time acidification of cytosol in these cells. It induced activation of mitophagy and autophagy in control and PD fibroblasts and protected against cell death. Importantly, the application of lactate to acute brain slices of control and Pink1 knockout mice also induced a reduction of pH in neurons and astrocytes that increase the level of mitophagy. Thus, acidification of cytosol by compounds which play important role in cell metabolism also can activate mitophagy and autophagy and protect cells in the familial form of PD.

Keywords: Parkinson's disease, mutations, mitophagy, autophagy

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Authors: P. Halder, A. Zaman

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It is estimated that heart disease accounts for one in ten deaths worldwide. United States deaths due to heart disease are among the leading causes of death according to the World Health Organization. Cardiovascular diseases (CVDs) account for one in four U.S. deaths, according to the Centers for Disease Control and Prevention (CDC). According to statistics, women are more likely than men to die from heart disease as a result of strokes. A 50% increase in men's mortality was reported by the World Health Organization in 2009. The consequences of cardiovascular disease are severe. The causes of heart disease include diabetes, high blood pressure, high cholesterol, abnormal pulse rates, etc. Machine learning (ML) can be used to make predictions and decisions in the healthcare industry. Thus, scientists have turned to modern technologies like Machine Learning and Data Mining to predict diseases. The disease prediction is based on four algorithms. Compared to other boosts, the Ada boost is much more accurate.

Keywords: heart disease, cardiovascular disease, coronary artery disease, feature selection, random forest, AdaBoost, SVM, decision tree

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Authors: Julia Gontar, Natalia Buderatskaya, Igor Ilyin, Olga Parnitskaya, Sergey Lavrynenko, Eduard Kapustin, Ekaterina Ilyina, Yana Lakhno

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Introduction: It is well known that oocytes obtained from older reproductive women have accumulated mitochondrial DNA mutations, which negatively affects the morphology of a developing embryo and may lead to the birth of a child with mitochondrial disease. Special techniques have been developed to allow a donor oocyte cytoplasmic transfer with the parents’ biological nuclear DNA retention. At the same time, it is important to understand whether the procedure affects the future embryonic chromosome sets as the nuclear DNA is the transfer subject in this new complex procedure. Material and Methods: From July 2015 to July 2016, the investigation was carried out in the Medical Centre IGR. 34 donor oocytes (group A) were used for the manipulation with the aim of donating cytoplasm: 21 oocytes were used for zygotes pronuclear transfer and oocytes 13 – for the spindle transfer. The mean age of the oocyte donors was 28.4±2.9 years. The procedure was performed using Nikon Ti Eclipse inverted microscope equipped with the micromanipulators Narishige system (Japan), Saturn 3 laser console (UK), Oosight imaging systems (USA). For the preimplantation genetic screening (PGS) blastocyst biopsy was performed, trophectoderm samples were diagnosed using fluorescent in situ hybridization on chromosomes 9, 13, 15, 16, 17, 18, 21, 22, X, Y. For comparison of morphological characteristics and euploidy, was chosen a group of embryos (group B) with the amount of 121 blastocysts obtained from 213 oocytes, which were gotten from the donor programs of assisted reproductive technologies (ART). Group B was not subjected to donor oocyte cytoplasmic transfer procedure and studied on the above mentioned chromosomes. Statistical analysis was carried out using the criteria t, x^2 at a significance levels p<0.05, p<0.01, p<0.001. Results: After the donor cytoplasm transfer process the amount of the third day developing embryos was 27 (79.4%). In this stage, the group B consisted of 189 (88.7%) developing embryos, and there was no statistically significant difference (SSD) between the two groups (p>0.05). After a comparative analysis of the morphological characteristics of the embryos on the fifth day, we also found no SSD among the studied groups (p>0.05): from 34 oocytes exposed to manipulation, 14 (41.2%) blastocysts was obtained, while the group B blastocyst yield was 56.8% (n=121) from 213 oocytes. The following results were obtained after PGS performing: in group A euploidy in studied chromosomes were 28.6%(n=4) blastocysts, whereas in group B this rate was 40.5%(n=49), 28.6%(n=4) and 21.5%(n=26) of mosaic embryos and 42.8%(n=6) and 38.0%(n=46) aneuploid blastocysts respectively were identified. None of these specified parameters had an SSD (p>0.05). But attention was drawn by the blastocysts in group A with identified mosaicism, which was chaotic without any cell having euploid chromosomal set, in contrast to the mosaic embryos in group B where identified chaotic mosaicism was only 2.5%(n=3). Conclusions: According to the obtained results, there is no direct procedural effect on the chromosome in embryos obtained following donor oocyte cytoplasmic transfer. Thus, the technology introduction will enhance the infertility treating effectiveness as well as avoiding having a child with mitochondrial disease.

Keywords: donor oocyte cytoplasmic transfer, embryos’ chromosome set, oocyte spindle transfer, pronuclear transfer

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Authors: N. V. Kazmiruk, Y. R. Nartsissov

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Phosphate activated glutaminase (GA, E.C. 3.5.1.2) plays a key role in glutamine/glutamate homeostasis in mammalian brain, catalyzing the hydrolytic deamidation of glutamine to glutamate and ammonium ions. GA is mainly localized in mitochondria, where it has the catalytically active form on the inner mitochondrial membrane (IMM) and the other soluble form, which is supposed to be dormant. At present time, the exact localization of the membrane glutaminase active site remains a controversial and an unresolved issue. The first hypothesis called c-side localization suggests that the catalytic site of GA faces the inter-membrane space and products of the deamidation reaction have immediate access to cytosolic metabolism. According to the alternative m-side localization hypothesis, GA orients to the matrix, making glutamate and ammonium available for the tricarboxylic acid cycle metabolism in mitochondria directly. In our study, we used a multi-compartment kinetic approach to simulate metabolism of glutamate and glutamine in the astrocytic cytosol and mitochondria. We used physiologically important ratio between the concentrations of glutamine inside the matrix of mitochondria [Glnₘᵢₜ] and glutamine in the cytosol [Glncyt] as a marker for precise functioning of the system. Since this ratio directly depends on the mitochondrial glutamine carrier (MGC) flow parameters, key observation was to investigate the dependence of the [Glnmit]/[Glncyt] ratio on the maximal velocity of MGC at different initial concentrations of mitochondrial glutamate. Another important task was to observe the similar dependence at different inhibition constants of the soluble GA. The simulation results confirmed the experimental c-side localization hypothesis, in which the glutaminase active site faces the outer surface of the IMM. Moreover, in the case of such localization of the enzyme, a 3-fold decrease in ammonium production was predicted.

Keywords: glutamate metabolism, glutaminase, kinetic approach, mitochondrial membrane, multi-compartment modeling

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Authors: Katherine Denise Queri

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The effects of sick workers have an impact in administration of labor. This study aims to provide knowledge on the disease that is Alzheimer’s while presenting an answer to the research question of when and how is the disease considered as a disaster inside the workplace. The study has the following as its research objectives: 1. Define Alzheimer’s disease, 2. Evaluate the effects and consequences of an employee suffering from Alzheimer’s disease, 3. Determine the concept of organizational effectiveness in the area of Human Resources, and 4. Identify common figures associated with Alzheimer’s disease. The researcher gathered important data from books, video presentations, and interviews of workers suffering from Alzheimer’s disease and from the internet. After using all the relevant data collection instruments mentioned, the following data emerged: 1. Alzheimer’s disease has certain consequences inside the workplace, 2. The occurrence of Alzheimer’s Disease in an employee’s life greatly affects the company where the worker is employed, and 3. The concept of workplace efficiency suggests that an employer must prepare for such disasters that Alzheimer’s disease may bring to the company where one is employed. Alzheimer’s disease can present disaster in any workplace.

Keywords: administration, Alzheimer's disease, conflict, disaster, employment

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Authors: Makhosi Buthelezi

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Mitochondrial DNA cytochrome c oxidase I (COI) gene analyses linked the South African groundnut leaf miner (GLM) to the Australian soya bean moth Aproaerema simplexella (Walker) and Indian Aproaerema modicella (Deventer). Thus, the genetic relatedness of GLM, A. simplexela, and A. modicella was examined by performing mitochondrial and nuclear (COI, cytochrome oxidase subunit II (COII), mitochondrial cytochrome b (CYTB), nuclear ribosomal 28S (28S) and intergenic spacer elongation factor-1 alpha ( EF-1 ALPHA) on 44 specimens collected from South Africa, four from Mozambique, and three each from single locations in India and Australia. Phylogenetic analyses were conducted using the Maximum Parsimony (MP) and Neighbour-Joining (NJ) methods. All of the datasets of the five DNA gene regions that were sequenced were also analyzed using the Basic Local Alignment Search Tool (BLAST) to find the closest matches for inclusion in the phylogenetic trees as outgroups and for purposes of information. In the phylogenetic trees for COI, COII, cytb and EF-1 ALPHA, a similar pattern was observed in the way that the sequences assembled into different groups; i.e., some sequences of A. simplexella from Australia were grouped separately from the others, but some Australian sequences grouped with those of the GLM from South Africa, India, and Mozambique. In the phylogenetic tree for 28S, all sequences from South Africa, Australia, India, and Mozambique grouped together and formed one group. For COI, genetic pairwise distance ranged from 0.97 to 3.60 %, for COII it ranged from 0.19% to 2.32%, for cytb it ranged from 0.25 to 9.77% and for EF-1 ALPHA it ranged 0.48 to 6.99%. Results of this study indicate that these populations are genetically related and presumably constitute a single species. Thus, further molecular and morphological studies need to be undertaken in order to resolve this apparent conundrum on the taxonomy of these populations.

Keywords: aproaerema modicella, aproaerema simplexella, mitochondrial DNA, nuclear DNA

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Authors: Reem Alajmi, Hind Al Harbi, Tahany Ayaad, Zainab Al Musawi

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Hard ticks Hyalomma spp. (family: Ixodidae) are obligate ectoparasite in their all life stages on some domestic animals mainly camels and cattle. Ticks may lead to many economic and public health problems because of their blood feeding behavior. Also, they act as vectors for many bacterial, viral and protozoan agents which may cause serious diseases such as tick-born encephalitis, Rocky-mountain spotted fever, Q-fever and Lyme disease which can affect human and/or animals. In the present study, molecular identification of ticks that attack camels in Riyadh region, Saudi Arabia based on the partial sequence of mitochondrial 16s rRNA gene was applied. Also, the present study aims to detect natural infections of collected camel ticks with Rickessia spp. and Borelia spp. using PCR/hybridization of Citrate synthase encoding gene present in bacterial cells. Hard ticks infesting camels were collected from different camels located in a farm in Riyadh region, Saudi Arabia. Results of the present study showed that the collected specimens belong to two species: Hyalomma dromedari represent 99% of the identified specimens and Hyalomma marginatum which account for 1 % of identified ticks. The molecular identification was made through blasting the obtained sequence of this study with sequences already present and identified in GeneBank. All obtained sequences of H. dromedarii specimens showed 97-100% identity with the same gene sequence of the same species (Accession # L34306.1) which was used as a reference. Meanwhile, no intraspecific variations of H. marginatum mesured because only one specimen was collected. Results also had shown that the intraspecific variability between individuals of H. dromedarii obtained in 92 % of samples ranging from 0.2- 6.6%, while the remaining 7 % of the total samples of H. dromedarii showed about 10.3 % individual differences. However, the interspecific variability between H. dromedarii and H. marginatum was approximately 18.3 %. On the other hand, by using the technique of PCR/hybridization, we could detect natural infection of camel ticks with Rickettsia spp. and Borrelia spp. Results revealed the natural presence of both bacteria in collected ticks. Rickettsial spp. infection present in 29% of collected ticks, while 35% of collected specimen were infected with Borrelia spp. The valuable results obtained from the present study are a new record for the molecular identification of camel ticks in Riyadh, Saudi Arabia and their natural infection with both Rickettsia spp. and Borrelia spp. These results may help scientists to provide a good and direct control strategy of ticks in order to protect one of the most important economic animals which are camels. Also results of this project spotlight on the disease that might be transmitted by ticks to put out a direct protective plan to prevent spreading of these dangerous agents. Further molecular studies are needed to confirm the results of the present study by using other mitochondrial and nuclear genes for tick identification.

Keywords: Camel ticks, Rickessia spp. , Borelia spp. , mitochondrial 16s rRNA gene

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Authors: Debasmita Dubey, Rajesh Kumar Meher, Smruti Pragya Samal, Pradeep Kumar Naik

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Background: To determine antioxidant properties and anticancer activity by ROS and mitochondrial transmembrane potential mediated apoptosis against MCF7, MDA-MB-231, cell line. Methods: Leaf sample was extracted using methanol by microwave digestion technique. The antioxidant properties of the methanolic extract were determined by a DPPH scavenging assay. In vitro anticancer activity, mitochondrial transmembrane potential, apoptosis activity and DNA fragmentation study, as well as intracellular ROS activity of most potential leaf extract, were also determined by using the MDA-MB-231cell line. In vivo animal toxicity study was carried out using mice model. Results: Methanolic leaf extract has shown the highest antioxidant, as well as anticancer activity, is based on the assay conducted. For the identification of active phytochemicals from methanolic extract, High-resolution mass spectroscopy-LCMS was used. In vitro cytotoxicity study against MCF-7 and MDA-MB-231 cell line and IC 50 value was found to be 37.5µg/ml. From histopathological studies, no toxicity in liver and kidney tissue was identified. Conclusion: This plant tuber can be used as a regular diet to reduce the chance of breast cancer. Further, more studies should be conducted to isolate and identify the responsible compound.

Keywords: human breast adenocarcinoma, ROS, mitochondrial transmembrane, apoptosis

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Authors: Ryan D. Martinus

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Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.

Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus

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Authors: Aneal Khan, Elleine Allapitan, Desmond Koo, Katherine-Ann Piedalue, Shaneel Pathak, Utkarsh Subnis

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Background: Disease management of metabolic, genetic disorders is long-term and can be cumbersome to patients and caregivers. Patient-Reported Outcome Measures (PROMs) have been a useful tool in capturing patient perspectives to help enhance treatment compliance and engagement with health care providers, reduce utilization of emergency services, and increase satisfaction with their treatment choices. Currently, however, PROMs are collected during infrequent and decontextualized clinic visits, which makes translation of patient experiences challenging over time. The GRIT study aims to evaluate a digital health journal application called Zamplo that provides a personalized health diary to record self-reported health outcomes accurately and efficiently in patients with metabolic, genetic disorders. Methods: This is a randomized controlled trial (RCT) (1:1) that assesses the efficacy of Zamplo to increase patient activation (primary outcome), improve healthcare satisfaction and confidence to manage medications (secondary outcomes), and reduce costs to the healthcare system (exploratory). Using standardized online surveys, assessments will be collected at baseline, 1 month, 3 months, 6 months, and 12 months. Outcomes will be compared between patients who were given access to the application versus those with no access. Results: Seventy-seven patients were recruited as of November 30, 2021. Recruitment for the study commenced in November 2020 with a target of n=150 patients. The accrual rate was 50% from those eligible and invited for the study, with the majority of patients having Fabry disease (n=48) and the remaining having Pompe disease and mitochondrial disease. Real-time clinical responses, such as pain, are being measured and correlated to disease-modifying therapies, supportive treatments like pain medications, and lifestyle interventions. Engagement with the application, along with compliance metrics of surveys and journal entries, are being analyzed. An interim analysis of the engagement data along with preliminary findings from this pilot RCT, and qualitative patient feedback will be presented. Conclusions: The digital self-care journal provides a unique approach to disease management, allowing patients direct access to their progress and actively participating in their care. Findings from the study can help serve the virtual care needs of patients with metabolic, genetic disorders in North America and the world over.

Keywords: eHealth, mobile health, rare disease, patient outcomes, quality of life (QoL), pain, Fabry disease, Pompe disease

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Authors: Ogbonnaya O. Iroanya, Samson T. Fakorede, Osamudiamen J. Edosa, Hadiat A. Azeez

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The human mitochondrial DNA (mtDNA) is about 17 kbp circular DNA fragments found within the mitochondria together with smaller fragments of 1200 bp known as the control region. Knowledge of variation within populations has been employed in forensic and molecular anthropology studies. The study was aimed at investigating the polymorphic nature of the two hypervariable segments (HVS) of the mtDNA, i.e., HVS1 and HVS2, and to determine the haplogroup distribution among individuals resident in Lagos, Southwestern Nigeria. Peripheral blood samples were obtained from sixty individuals who are not related maternally, followed by DNA extraction and amplification of the extracted DNA using primers specific for the regions under investigation. DNA amplicons were sequenced, and sequenced data were aligned and compared to the revised Cambridge Reference Sequence (rCRS) GenBank Accession number: NC_012920.1) using BioEdit software. Results obtained showed 61 and 52 polymorphic nucleotide positions for HVS1 and HVS2, respectively. While a total of three indels mutation were recorded for HVS1, there were seven for HVS2. Also, transition mutations predominate nucleotide change observed in the study. Genetic diversity (GD) values for HVS1 and HVS2 were estimated to be 84.21 and 90.4%, respectively, while random match probability was 0.17% for HVS1 and 0.89% for HVS2. The study also revealed mixed haplogroups specific to the African (L1-L3) and the Eurasians (U and H) lineages. New polymorphic sites obtained from the study are promising for human identification purposes.

Keywords: hypervariable region, indels, mitochondrial DNA, polymorphism, random match probability

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Authors: Olusola Olalekan Elekofehinti, Isaac Gbadura Adanlawo, Joao Batista Teixeira Rocha

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We evaluated the potential neuroprotective effect of Phyllantus nuriri against Fe2+ and SNP induced oxidative stress in mitochondria of rats brain. Cellular viability was assessed by MTT reduction, reactive oxygen species (ROS) generation was measured using the probe 2,7-dichlorofluorescein diacetate (DCFH-DA). Glutathione content was measured using dithionitrobenzoic acid (DTNB). Fe2+ (10µM) and SNP (5µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, this occurred in parallel with increased glutathione oxidation, ROS production and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with methanolic extract of Phyllantus nuriri (10-100 µg/ml) reduced the disruption of mitochondrial activity, gluthathione oxidation, ROS production as well as the increase in TBARS levels caused by both Fe2+ and SNP in a dose dependent manner. HPLC analysis of the extract revealed the presence of gallic acid (20.54±0.01), caffeic acid (7.93±0.02), rutin (25.31±0.05), quercetin (31.28±0.03) and kaemferol (14.36±0.01). This result suggests that these phytochemicals account for the protective actions of Phyllantus nuriri against Fe2+ and SNP -induced oxidative stress. Our results show that Phyllantus nuriri consist important bioactive molecules in the search for an improved therapy against the deleterious effects of Fe2+, an intrinsic producer of reactive oxygen species (ROS), that leads to neuronal oxidative stress and neurodegeneration.

Keywords: Phyllantus niruri, neuroprotection, oxidative stress, mitochondria, synaptosome

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Authors: Shahzad Bhattiab, M. Aslamkhana, Sana Abbasbc, Marcella Attimonellid, Kumarasamy Thangaraje, Erica Martinha Silva de Souzaf, Uzay U. Sezen

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The present study was designed to investigate three regions of mitochondrial DNA, HVI, HVII and HVIII, to hold a powwow genetic diversity and affiliations in 115 probands of 6 major ethnic groups, viz., Bijarani, Chandio, Ghallu, Khoso, Nasrani and Solangi, in the province of Sindh of Pakistan. For this purpose 88 haplotypes were scrutinized, defined by particular set of nucleotides (ignoring the C insertions around position 309 and 315). In spite of that 82% sequences were observed once, 12 % twice and 5.2 % thrice. The most common South Asian haplotypes were observed M (42%), N (6.9%) and R (6.9%) whereas west Eurasian haplotypes were J (1.7%), U (23.4%), H (9.5%), W (6.9%) and T (0.86%), in six ethnic groups. A random match probability between two unrelated individuals was found 0.06 %, while genetic diversity was ranged to be 0.991 to 0.999, and nucleotide diversity ranged from 0.0089 to 0.0142 for the whole control region of the population studied.

Keywords: mtDNA haplogroups, control region, Pakistan, Sindh, ethnicity

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Authors: Asim Abbasi, Amer Habib, Sajid Hussain, Muhammad Sufyan, Iqra, Hasnain Sajjad

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Except for few scattered cases, powdery mildew disease was not a big problem for watermelon in the past but with the outbreaks of its pathotypes, races 1W and 2W, this disease becomes a serious issue all around the globe. The severe outbreak of this disease also increased the rate of fungicide application for its proper management. Twelve varieties of watermelon were screened in Research Area of Department of Plant pathology, University of Agriculture, Faisalabad to check the incidence of powdery mildew disease. Disease inoculum was prepared and applied with the help of foliar spray method. Fungicides and plants extracts were also applied after the disease incidence. Percentage leaf surface area diseased was assessed visually with a modified Horsfall-Barratt scale. The results of the experiment revealed that among all varieties, WT2257 and Zcugma F1 were highly resistant showing less than 5% disease incidence while Anar Kali and Sugar baby were highly susceptible with disease incidence of more than 65%. Among botanicals neem extract gave best results with disease incidence of less than 20%. Besides neem, all other botanicals also gave significant control of powdery mildew disease than the untreated check. In case of fungicides, Gemstar showed least disease incidence i.e. < 10%, however besides control maximum disease incidence was observed in Curzate (> 30%).

Keywords: botanicals, fungicides, pathotypes, powdery mildew

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Authors: Syed Dawood M. Taimur

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Background: Peripheral arterial disease (PAD) is under diagnosed in primary care practices, yet the extent of unrecognized PAD in patients with coronary artery disease (CAD) is unknown. Objective: To assess the prevalence of previously unrecognized PAD in patients undergoing coronary angiogram and to determine the relationship between the presence of PAD and severity of CAD. Material & Methods: This five years retrospective study was conducted at an invasive lab of the department of Cardiology, Ibrahim Cardiac Hospital & Research Institute from January 2010 to December 2014. Total 77 patients were included in this study. Study variables were age, sex, risk factors like hypertension, diabetes mellitus, dyslipidaemia, smoking habit and positive family history for ischemic heart disease, coronary artery and peripheral artery profile. Results: Mean age was 56.83±13.64 years, Male mean age was 53.98±15.08 years and female mean age was 54.5±1.73years. Hypertension was detected in 55.8%, diabetes in 87%, dyslipidaemia in 81.8%, smoking habits in 79.2% and 58.4% had a positive family history. After catheterization 88.3% had peripheral arterial disease and 71.4% had coronary artery disease. Out of 77 patients, 52 had both coronary and peripheral arterial disease which was statistically significant (p < .014). Coronary angiogram revealed 28.6% (22) patients had triple vessel disease, 23.3% (18) had single vessel disease, 19.5% (15) had double vessel disease and 28.6% (22) were normal coronary arteries. The peripheral angiogram revealed 54.5% had superficial femoral artery disease, 26% had anterior tibial artery disease, 27.3% had posterior tibial artery disease, 20.8% had common iliac artery disease, 15.6% had common femoral artery disease and 2.6% had renal artery disease. Conclusion: There is a strong and definite correlation between coronary and peripheral arterial disease. We found that cardiovascular risk factors were in fact risk factors for both PAD and CAD.

Keywords: coronary artery disease (CAD), peripheral artery disease(PVD), risk, factors, correlation, cathetarization

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Authors: Aslı Şalcıoğlu, Grigorous Krey, Raşit Bilgin

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In this study, the effect of the Turkish Straits System (TSS), comprising a biogeographical boundary that forms the connection between the Mediterranean and the Black Sea, on the evolutionary history, phylogeography and intraspecific gene flow of the whiting (Merlangius merlangus) a demersal fish species, was investigated. For these purposes, the mitochondrial DNA (CO1, cyt-b) genes were used. In addition, genetic comparisons samples from other regions (Greece, France, Atlantic) obtained from GenBank and Barcode of Life Database were made to better understand the phylogeographic history of the species at a larger geographic scale. Within this study, high level of genetic differentiation was observed along the Turkish coastal waters based on cyt-b gene, suggesting that TSS is a barrier to dispersal. Two different sub-species were also observed based on mitochondrial DNA, one found in Turkish coastal waters and Greece (M.m euxinus) and other (M.m. merlangus) in Atlantic, France.

Keywords: genetic, phylogeography, TSS, whiting

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Authors: Jiaojiao Zhang

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Boar sperm quality, as an important indicator of reproductive efficiency, directly affects the efficiency of livestock production. Here, this study was conducted to improve the boar sperm quality by using a non-thermal dielectric barrier discharge (DBD) plasma. Our results showed that DBD plasma exposure at 2.1 W for 15 s could improve boar sperm quality by increasing the exon methylation level of adenosine monophosphate-activated protein kinase (AMPK) and thus improving the glycolytic flux, mitochondrial function, and antioxidant capacity without damaging the integrity of sperm DNA and acrosome. In addition, DBD plasma could rescue DNA methyltransferase inhibitor decitabine-caused low sperm quality by reducing oxidative stress and mitochondrial damage. Therefore, the application of non-thermal plasma provides a new strategy for reducing sperm oxidative damage and improving sperm quality, which shows great potential in assisted reproduction to solve the problem of male infertility.

Keywords: non-thermal DBD plasma, sperm quality, AMPK methylation, energy metabolism, antioxidant capacity

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Authors: W. Soufi, F. Boukli Hacene, S. Ghalem

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Alzheimer's disease (AD) is a neurodegenerative disease that leads to a progressive and permanent deterioration of nerve cells. This disease is progressively accompanied by an intellectual deterioration leading to psychological manifestations and behavioral disorders that lead to a loss of autonomy. It is the most frequent of degenerative dementia. Alzheimer's disease (AD), which affects a growing number of people, has become a major public health problem in a few years. In the context of the study of the mechanisms governing the evolution of AD disease, we have found that natural flavonoids are good acetylcholinesterase inhibitors that reduce the rate of ßA secretion in neurons. This work is to study the inhibition of acetylcholinesterase (AChE) which is an enzyme involved in Alzheimer's disease, by methods of molecular modeling. These results will probably help in the development of an effective therapeutic tool in the fight against the development of Alzheimer's disease. Our goal of the research is to study the inhibition of acetylcholinesterase (AChE) by molecular modeling methods.

Keywords: Alzheimer's disease, acetylcholinesterase, flavonoids, molecular modeling

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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