Evolutionary genomics analysis of human nucleus-encoded mitochondrial genes: implications for the roles of energy production and metabolic pathways in the pathogenesis and pathophysiology of demyelinating diseases

Publication date: Available online 12 November 2019Source: Neuroscience LettersAuthor(s): Yunyun Shen, Xuan Wang, Shenyuan Guo, Mengsheng Qiu, Gonglin Hou, Zhou TanABSTRACTThe myelin sheath is a plasma membrane extension that lines nerve fibers to protect, support and insulate neurons. The myelination of axons in vertebrates enables fast, saltatory impulse propagation, and this process relies on organelles, especially on mitochondria to supply energy. Approximately 99% of mitochondrial proteins are encoded in the nucleus. Since mitochondria play a central role in the energy production and metabolic pathways, which are essential for myelinogenesis, studying these nucleus-encoded genes (nMGs) may provide new insights into the roles of energy metabolism in demyelinating diseases. In this work, a multiomics-based approach was employed to 1) construct a 1,740 human nMG subset with mitochondrial localization evidence obtained from the Integrated Mitochondrial Protein Index (IMPI) and MitoCarta databases, 2) conduct an evolutionary genomics analysis across mouse, rat, monkey, chimp, and human models, 3) examine dysmyelination phenotype-related genes (nMG subset genes with oligodendrocyte- ​and myelin-related ​phenotypes, OMP-nMGs) in MGI mouse lines and human patients, 4) determine the expression discrepancy of OMP-nMGs in brain tissues of cuprizone-treated mice, multiple sclerosis patients, and normal controls, and 5) conduct literature data mining to explore OMP-nMG-associated...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research

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In this study, human multiple sclerosis and mice brain samples were analyzed through mass spectrometry as well as histological and immunoblot techniques, which demonstrated that iron deposition is associated with increased levels of nuclear prelamin A recognition factor (NARF). NARF is a protein associated with the mitochondria which has also been linked to mitochondrial defects in multiple sclerosis. We report NARF to be associated in multiple sclerosis pathology and aberrant iron deposition.
Source: Metabolic Brain Disease - Category: Neurology Source Type: research
CONCLUSIONOur findings suggest that CSF levels of the NLRP3 inflammasome may serve as a diagnostic biomarker for distinguishing NMOSD and MS. Pyroptosis mediated by the NLRP3 inflammasome following mitochondrial damage may play an important role in the pathogenesis of these neuroinflammatory disorders, especially NMOSD.Graphical abstract
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Monica R. Langley, Hyesook Yoon, Ha-Neui Kim, Chan-Il Choi, Whitney Simon, Laurel Kleppe, Ian R. Lanza, Nathan K. LeBrasseur, Aleksey Matveyenko, Isobel A. ScarisbrickAbstractMetabolic syndrome is a key risk factor and co-morbidity in multiple sclerosis (MS) and other neurological conditions, such that a better understanding of how a high fat diet contributes to oligodendrocyte loss and the capacity for myelin regeneration has the potential to highlight new treatment targets. Results demonstr...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Publication date: Available online 5 December 2019Source: CellAuthor(s): Chun-Cheih Chao, Cristina Gutiérrez-Vázquez, Veit Rothhammer, Lior Mayo, Michael A. Wheeler, Emily C. Tjon, Stephanie E.J. Zandee, Manon Blain, Kalil Alves de Lima, Maisa C. Takenaka, Julian Avila-Pacheco, Patrick Hewson, Lei Liu, Liliana M. Sanmarco, Davis M. Borucki, Gabriel Z. Lipof, Sunia A. Trauger, Clary B. Clish, Jack P. Antel, Alexandre PratSummaryMetabolism has been shown to control peripheral immunity, but little is known about its role in central nervous system (CNS) inflammation. Through a combination of proteomic, metabolomi...
Source: Cell - Category: Cytology Source Type: research
Authors: Seo DY, Heo JW, Ko JR, Kwak HB Abstract Neuroinflammation is a central pathological feature of several acute and chronic brain diseases, including Alzheimer disease (AD), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). It induces microglia activation, mitochondrial dysfunction, the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), pro-inflammatory cytokines, and reactive oxygen species. Exercise, which plays an important role in maintaining and improving brain health, might be a highly effective intervention for preventing ...
Source: International Neurourology Journal - Category: Urology & Nephrology Tags: Int Neurourol J Source Type: research
Abstract Neurodegenerative disease refers to a range of chronic and progressive disorders that are characterized by dysfunction and loss of neurons. Neurodegeneration involves protein misfolding, oxidative injury, impaired mitochondrial function, neurotrophin deficiency and may also involve neuroinflammation. The sirtuin family of proteins plays a key role in this process suggesting that modulation of sirtuin can modify disease progression. This review examines experimental and clinical evidence relating to the potential role of SIRT1 and SIRT2, and their modulators in neurodegenerative diseases. Both neuroprotect...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
In conclusion, T2D impairs vascular function by dysregulated autophagy. Therefore, autophagy could be a potential target for overcoming diabetic microvascular complications. To What Degree Does Loss of Skeletal Muscle with Age Contribute to Immunosenescence? https://www.fightaging.org/archives/2019/11/to-what-degree-does-loss-of-skeletal-muscle-with-age-contribute-to-immunosenescence/ Sarcopenia, the progressive loss of muscle mass and strength, is characteristic of aging. A perhaps surprisingly large fraction of the losses can be averted by strength training, but there are nonetheless inexorable process...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Women have increased prevalence of Th17-mediated autoimmune diseases, including lupus and multiple sclerosis, and severe asthma. While estradiol and progesterone increased IL-17A production in Th17 cells by inhibiting Let7f miRNA expression and increasing IL-23 receptor (IL-23R) expression, it remained unclear how estrogen signaling through the canonical nuclear receptors, estrogen receptor α (ERα) and/or ERβ, regulated this pathway. We hypothesized that estrogen signaling through ERα increased IL-23R expression and IL-17A production from Th17 cells. To test this hypothesis, naïve T cells from W...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract The complex scenario of multiple sclerosis (MS) pathology involves several mechanisms, including oxidative stress response. The heat shock proteins (HSPs) are important for the protection of the cells; however, their role in MS is not clear. The present research is focused on the response of peripheral blood mononuclear cells (PBMCs) to oxidative stress and to the involvement of HSP70-2 (a protein coded by the HSPA1B gene, located in the MHC class III). To this aim, we challenged PBMCs from MS patients and healthy controls with hydrogen peroxide. Specifically, PBMCs mitochondrial activity, HSP70-2 protein...
Source: Cell Stress and Chaperones - Category: Cytology Authors: Tags: Cell Stress Chaperones Source Type: research
Conclusion: The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
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