Role of Sirt1 During the Ageing Process: Relevance to Protection of Synapses in the Brain

Godoy, J.A.; Zolezzi J.M.; Braidy, N; Inestrosa, N. C.

Abstract

Ageing is a stochastic process associated with a progressive decline in physiological functions which predispose to the pathogenesis of several neurodegenerative diseases. The intrinsic complexity of ageing remains a significant challenge to understand the cause of this natural phenomenon. At the molecular level, ageing is thought to be characterized by the accumulation of chronic oxidative damage to lipids, proteins and nucleic acids caused by free radicals. Increased oxidative stress and misfolded protein formations, combined with impaired compensatory mechanisms, may promote neurodegenerative disorders with age. Nutritional modulation through calorie restriction has been shown to be effective as an anti-ageing factor, promoting longevity and protecting against neurodegenerative pathology in yeast, nematodes and murine models. Calorie restriction increases the intracellular levels of the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD(+)), a co-substrate for the sirtuin 1 (Sirt1, silent mating-type information regulator 2 homolog 1) activity and a cofactor for oxidative phosphorylation and ATP synthesis. Promotion of intracellular NAD(+) anabolismis speculated to induce neuroprotective effects against amyloid-beta-peptide (A beta) toxicity in some models for Alzheimer's disease (AD). The NAD(+)-dependent histone deacetylase, Sirt1, has been implicated in the ageing process. Sirt1 serves as a deacetylase for numerous proteins involved in several cellular pathways, including stress response and apoptosis, and plays a protective role in neurodegenerative disorders, such as AD.

Más información

Título según WOS: Role of Sirt1 During the Ageing Process: Relevance to Protection of Synapses in the Brain
Título según SCOPUS: Role of Sirt1 During the Ageing Process: Relevance to Protection of Synapses in the Brain
Título de la Revista: MOLECULAR NEUROBIOLOGY
Volumen: 50
Número: 3
Editorial: Springer
Fecha de publicación: 2014
Página de inicio: 744
Página final: 756
Idioma: English
URL: http://link.springer.com/10.1007/s12035-014-8645-5
DOI:

10.1007/s12035-014-8645-5

Notas: ISI, SCOPUS - ISI