Deciphering therapeutic options for neurodegenerative diseases: insights from SIRT1

J Mol Med (Berl). 2022 Apr;100(4):537-553. doi: 10.1007/s00109-022-02187-2. Epub 2022 Mar 11.

Abstract

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD +)-dependent protein deacetylase that exerts biological effects through nucleoplasmic transfer. Recent studies have highlighted that SIRT1 deacetylates protein substrates to exert its neuroprotective effects, including decreased oxidative stress and inflammatory, increases autophagy, increases levels of nerve growth factors (correlated with behavioral changes), and maintains neural integrity (affects neuronal development and function) in aging or neurological disorder. In this review, we highlight the molecular mechanisms underlying the protective role of SIRT1 in modulating neurodegeneration, focusing on protein homeostasis, aging-related signaling pathways, neurogenesis, and synaptic plasticity. Meanwhile, the potential of targeting SIRT1 to block the occurrence and progression of neurodegenerative diseases is also discussed. Taken together, this review provides an up-to-date evaluation of our current understanding of the neuroprotective mechanisms of SIRT1 and also be involved in the potential therapeutic opportunities of AD and related neurodegenerative diseases.

Keywords: Aging; Neurodegenerative diseases; Neurogenesis; Protein homeostasis; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / therapy
  • Neurogenesis
  • Signal Transduction
  • Sirtuin 1 / metabolism

Substances

  • SIRT1 protein, human
  • Sirtuin 1