Nimmagadda Vamshi K C, Makar Tapas K, Chandrasekaran Krish, Sagi Avinash Rao, Ray Jayanta, Russell James W, Bever Christopher T
Department of Neurology, University of Maryland, Baltimore, MD 21201, USA; Research Service, VA Maryland Health Care System, Baltimore, MD 21201, USA.
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.
J Neuroimmunol. 2017 Mar 15;304:29-34. doi: 10.1016/j.jneuroim.2016.07.007. Epub 2016 Jul 17.
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.
神经退行性变是多发性硬化症（MS）导致残疾的一个重要决定因素，但尽管目前已获批的治疗方法可减轻炎症，却尚未证实它们能减少神经退行性变。SIRT1是一种依赖烟酰胺腺嘌呤二核苷酸（NAD）的蛋白质脱乙酰酶，已被认为与包括MS在内的神经疾病中神经退行性变的发病机制有关。我们研究了SIRT1在实验性自身免疫性脑脊髓炎（EAE）中的作用，并发现了其具有神经保护作用的证据。在本综述中，我们总结了在转基因小鼠中使用SIRT1激活剂和SIRT1过表达的最新研究结果。这些数据为在MS中使用SIRT1激活剂提供了理论依据。
