About: SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease

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About: SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease
Creator	Das Sarma, Jayasri Dine, Kimberly Khan, Reas Shindler, Kenneth
source	Medline; PMC
abstract	BACKGROUND: Multiple sclerosis (MS) is characterized by central nervous system inflammation and demyelination, and increasing evidence demonstrates significant neuronal damage also occurs and is associated with permanent functional impairment. Current MS therapies have limited ability to prevent neuronal damage, suggesting additional neuroprotective therapies are needed. Compounds that activate the NAD(+)-dependent SIRT1 deacetylase prevent neuronal loss in an autoimmune-mediated MS model, but the mechanism of this effect is unknown, and it is unclear whether SIRT1 activating compounds exert similar effects in demyelinating disease induced by other etiologies. We measured neuronal loss in C57BL/6 mice inoculated with a neurotropic strain of mouse hepatitis virus, MHV-A59, that induces an MS-like disease. RESULTS: Oral treatment with the SIRT1 activating compound SRTAW04 significantly increased SIRT1 activity within optic nerves and prevented neuronal loss during optic neuritis, an inflammatory demyelinating optic nerve lesion that occurs in MS and its animal models. MHV-A59 induced neuronal loss was associated with reactive oxygen species (ROS) accumulation, and SRTAW04 treatment significantly reduced ROS levels while promoting increased expression of enzymes involved in mitochondrial function and reduction of ROS. SRTAW04 exerted similar protective effects in EAE spinal cords, with decreased demyelination. CONCLUSIONS: Results demonstrate that SIRT1 activating compounds prevent neuronal loss in viral-induced demyelinating disease similar to their effects in autoimmune-mediated disease. One mechanism of this neuroprotective effect involves increasing mitochondrial biogenesis with reduction of oxidative stress. SIRT1 activators represent a potential neuroprotective therapy for MS. Understanding common mechanisms of these effects in distinct disease models will help identify targets for more specific therapies.
has issue date	2014-01-02(xsd:dateTime)
bibo:doi	10.1186/2051-5960-2-3
bibo:pmid	24383546
has license	cc-by
sha1sum (hex)	ab906d73fa3fecf440ed8c98ad852397bf7bee1f
schema:url	https://doi.org/10.1186/2051-5960-2-3
resource representing a document's title	SIRT1 Activating compounds reduce oxidative stress mediated neuronal loss in viral induced CNS demyelinating disease
has PubMed Central identifier	PMC3892130
has PubMed identifier	24383546
schema:publication	Acta Neuropathol Commun
resource representing a document's body	covid:ab906d73fa3fecf440ed8c98ad852397bf7bee1f#body_text
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