Mitochondrial DNA Copy Number in Peripheral Blood as a Potential Non-invasive Biomarker for Multiple Sclerosis

AbstractThe impaired mitochondrial function has been implicated in the pathogenicity of multiple sclerosis  (MS), a chronic inflammatory, demyelinating, and neurodegenerative disease of the CNS. Circulating mtDNA copy number in body fluids has been proposed as an indicator for several neurodegenerative diseases, and the altered cerebrospinal fluid mtDNA has been shown as a promising marker for MS. Th e aim of this study was to determine changes and biomarker potential of circulating mtDNA in peripheral blood in MS. The mtDNA copy number was quantified by real-time PCR in blood samples from 60 patients with relapsing–remitting MS (RRMS) and 64 healthy controls. The RRMS patients had significant ly lower circulating mtDNA copy number compared to controls. Subgroup analysis with stratification of RRMS patients based on disease duration under or over 10 years revealed that the mtDNA copy number was significantly lower in the group with longer disease duration. A negative correlation was obse rved between mtDNA copy number and disease duration. The ROC curve analysis indicated a significant ability of mtDNA copy number to separate RRMS patients from controls with an AUC of 0.859. This is the first study to measure peripheral blood mtDNA copy number in MS patients. Current data suggest th at the reduction in peripheral blood mtDNA copy number may be an early event in MS and correlate with the disease progression. The findings of this study indicate th...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research

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Abstract Retrotransposon activation occurs in a variety of neurological disorders including multiple sclerosis and Alzheimer's Disease. While the origins of disease-related retrotransposon activation have remained mostly unidentified, this phenomenon may well contribute to disease progression by inducing inflammation, disrupting transcription and, potentially, genomic insertion. Here, we report that the inhibition of mitochondrial respiratory chain complex I by pharmacological agents widely used to model Parkinson's disease leads to a significant increase in expression of the ORF1 protein of the long interspersed ...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
Publication date: Available online 25 February 2020Source: Multiple Sclerosis and Related DisordersAuthor(s): Ayelet Armon-Omer, Hadar Neuman, Adi Sharabi-Nov, Radi Shahien
Source: Multiple Sclerosis and Related Disorders - Category: Neurology Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, targeting the dysfunctional complex I usingNDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.
Source: Molecular Neurobiology - Category: Neurology Source Type: research
e;ma M, Slanař O Abstract Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination and axonal damage and resulting in a range of physical, mental or even psychiatric symptoms. Key role of oxidative stress (OS) in the pathogenesis of MS has been suggested, as indicated by the biochemical analysis of cerebrospinal fluid and blood samples, tissue homogenates, and animal models of multiple sclerosis. OS causes demyelination and neurodegeneration directly, by oxidation of lipids, proteins and DNA but also indirectl...
Source: Physiological Research - Category: Physiology Authors: Tags: Physiol Res Source Type: research
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
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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
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