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Neurochem Res. 2017 Mar;42(3):876-890. doi: 10.1007/s11064-016-2110-y. Epub 2016 Nov 24.

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

Author information

1
Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego st., 02106, Warsaw, Poland.
2
Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego st., 02106, Warsaw, Poland.
3
Laboratory of Preclinical Research and Environmental Agents, Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego st., 02106, Warsaw, Poland. rstrosznajder@imdik.pan.pl.

Abstract

Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD+ levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD+-dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

KEYWORDS:

Alzheimer’s disease; Brain aging; Neuroprotection; Parkinson’s disease; Sirtuins; Transcription factors

PMID:
27882448
PMCID:
PMC5357501
DOI:
10.1007/s11064-016-2110-y
[Indexed for MEDLINE]
Free PMC Article

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