The protective effects of activating Sirt1/NF-κB pathway for neurological disorders

Rev Neurosci. 2021 Nov 8;33(4):427-438. doi: 10.1515/revneuro-2021-0118. Print 2022 Jun 27.

Abstract

Sirt1, a member of the sirtuins family, is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase. It can be involved in the regulation of several processes including inflammatory response, apoptosis, oxidative stress, energy metabolism, and autophagy by exerting deacetylation. Nuclear factor-κB (NF-κB), a crucial nuclear transcription factor with specific DNA binding sequences, exists in almost all cells and plays a vital role in several biological processes involving inflammatory response, immune response, and apoptosis. As the hub of multiple intracellular signaling pathways, the activity of NF-κB is regulated by multiple factors. Sirt1 can both directly deacetylate NF-κB and indirectly through other molecules to inhibit its activity. We would like to emphasize that Sirt1/NF-κB is a signaling pathway that is closely related to neuroinflammation. Many recent studies have demonstrated the neuroprotective effects of Sirt1/NF-κB signaling pathway activation applied to the treatment of neurological related diseases. In this review, we focus on new advances in the neuroprotective effects of the Sirt1/NF-κB pathway. First, we briefly review Sirt1 and NF-κB, two key molecules of cellular metabolism. Next, we discuss the connection between NF-κB and neuroinflammation. In addition, we explore how Sirt1 regulates NF-κB in nerve cells and relevant evidence. Finally, we analyze the therapeutic effects of the Sirt1/NF-κB pathway in several common neuroinflammation-related diseases.

Keywords: NF-κB; Sirt1; neuroinflammation; neurological disorders; treatment.

Publication types

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

MeSH terms

  • Humans
  • NF-kappa B / metabolism
  • Nervous System Diseases*
  • Neuroprotective Agents* / pharmacology
  • Signal Transduction
  • Sirtuin 1 / metabolism

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • SIRT1 protein, human
  • Sirtuin 1