SIRT1 in Neurodevelopment and Brain Senescence
Author(s)Herskovits, A. Zara; Guarente, Leonard Pershing
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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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Glenn Laboratory for the Science of Aging
Herskovits, A. Zara, and Leonard Guarente. “SIRT1 in Neurodevelopment and Brain Senescence.” Neuron 81, no. 3 (February 2014): 471–483. © 2014 Elsevier Inc.
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