神经保护
西妥因1
锡尔图因
生物
神经退行性变
白藜芦醇
神经科学
瓦勒氏变性
转录因子
细胞生物学
调节器
NAD+激酶
药理学
基因
疾病
生物化学
下调和上调
医学
内科学
酶
作者
Bor Luen Tang,Christelle En Lin Chua
标识
DOI:10.1016/j.mam.2007.02.001
摘要
SIRT1 is the mammalian homologue of yeast silent information regulator (Sir)-2, a member of the sirtuin family of protein deacetylases which have gained much attention as mediators of lifespan extension in several model organisms. Induction of SIRT1 expression also attenuates neuronal degeneration and death in animal models of Alzheimer's disease and Huntington's disease. SIRT1 induction, either by sirtuin activators such as resveratrol, or metabolic conditioning associated with caloric restriction (CR), could be neuroprotective in several ways. It could promote the non-amyloidogenic cleavage of the amyloid precursor protein, enhance clearance of amyloid beta-peptides, and reduced neuronal damage through potential inhibition of neuroinflammatory signaling pathways. In addition, increased SIRT1 activity could alter neuronal transcription profiles to enhance anti-stress and anti-apoptotic gene activities, and has been proposed to underlie the inhibition of axonal degeneration in the Wallerian degeneration slow (Wld(s)) phenotype. As neuronal degeneration is a major pathophysiological aspect of human aging, understanding the mechanism of SIRT1 neuroprotection promises novel strategies in clinical intervention of neurodegenerative diseases.
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