SIRT1 in Neurodevelopment and Brain Senescence

被引：508

作者：

Herskovits, A. Zara ^{[1
,2
,3
]}

Guarente, Leonard ^{[2
,3
,4
]}

机构：

[1] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] MIT, Glenn Labs Sci Aging, Cambridge, MA 02139 USA

[4] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

来源：

NEURON | 2014年 / 81卷 / 03期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; BULBAR MUSCULAR-ATROPHY; FRONTOTEMPORAL LOBAR DEGENERATION; DEPENDENT PROTEIN DEACETYLASES; TRANSGENIC MOUSE MODEL; DIET-INDUCED OBESITY; HISTONE DEACETYLASE; CALORIE RESTRICTION; HUNTINGTONS-DISEASE; SACCHAROMYCES-CEREVISIAE;

D O I：

10.1016/j.neuron.2014.01.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent deacylases that have traditionally been linked with calorie restriction and aging in mammals. These proteins also play an important role in maintaining neuronal health during aging. During neuronal development, the SIR2 ortholog SIRT1 is structurally important, promoting axonal elongation, neurite outgrowth, and dendritic branching. This sirtuin also plays a role in memory formation by modulating synaptic plasticity. Hypothalamic functions that affect feeding behavior, endocrine function, and circadian rhythmicity are all regulated by SIRT1. Finally, SIRT1 plays protective roles in several neurodegenerative diseases including Alzheimer's, Parkinson's, and motor neuron diseases, which may relate to its functions in metabolism, stress resistance, and genomic stability. Drugs that activate SIRT1 may offer a promising approach to treat these disorders.

引用

页码：471 / 483

页数：13

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