SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

Vamshi K C Nimmagadda; Tapas K Makar; Krish Chandrasekaran; Avinash Rao Sagi; Jayanta Ray; James W Russell; Christopher T Bever Jr

doi:10.1016/j.jneuroim.2016.07.007

SIRT1 and NAD+ precursors: Therapeutic targets in multiple sclerosis a review

J Neuroimmunol. 2017 Mar 15:304:29-34. doi: 10.1016/j.jneuroim.2016.07.007. Epub 2016 Jul 17.

Authors

Vamshi K C Nimmagadda¹, Tapas K Makar², Krish Chandrasekaran³, Avinash Rao Sagi³, Jayanta Ray³, James W Russell¹, Christopher T Bever Jr⁴

Affiliations

¹ Department of Neurology, University of Maryland, Baltimore, MD 21201, USA; Research Service, VA Maryland Health Care System, Baltimore, MD 21201, USA.
² Department of Neurology, University of Maryland, Baltimore, MD 21201, USA; Research Service, VA Maryland Health Care System, Baltimore, MD 21201, USA; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, USA.
³ Department of Neurology, University of Maryland, Baltimore, MD 21201, USA.
⁴ Department of Neurology, University of Maryland, Baltimore, MD 21201, USA; Research Service, VA Maryland Health Care System, Baltimore, MD 21201, USA; VA Multiple Sclerosis Center of Excellence East, Baltimore, MD 21201, USA. Electronic address: [email protected].

Abstract

Neurodegeneration is an important determinant of disability in multiple sclerosis (MS) but while currently approved treatments reduce inflammation, they have not been shown to reduce neurodegeneration. SIRT1, a NAD dependent protein deacetylase, has been implicated in the pathogenesis of neurodegeneration in neurological diseases including MS. We have studied the role of SIRT1 in experimental autoimmune encephalomyelitis (EAE) and found evidence for a neuroprotective role. In this review we summarize the most recent findings from the use of SIRT1 activators and SIRT1 overexpression in transgenic mice. These data support provide a rational for the use of SIRT1 activators in MS.

Keywords: EAE; Multiple sclerosis; NAD; Neurodegeneration; SIRT1.

Published by Elsevier B.V.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Encephalomyelitis, Autoimmune, Experimental / drug therapy
Encephalomyelitis, Autoimmune, Experimental / metabolism
Humans
Immunosuppressive Agents / therapeutic use
Multiple Sclerosis / drug therapy
Multiple Sclerosis / metabolism*
NAD / biosynthesis*
Sirtuin 1 / biosynthesis*

Substances

Immunosuppressive Agents
NAD
SIRT1 protein, human
Sirtuin 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding