Role of RhoA/ROCK signaling in Alzheimer's disease

Behav Brain Res. 2021 Sep 24:414:113481. doi: 10.1016/j.bbr.2021.113481. Epub 2021 Jul 21.

Abstract

Rho-associated coiled-coil kinase (ROCK), a serine/threonine kinase regulated by the small GTPase RhoA, is involved in regulating cell migration, proliferation, and survival. Numerous studies have shown that the RhoA/ROCK signaling pathway can promote Alzheimer's disease (AD) occurrence. ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. This is suggestive of a possible positive feedback role for Aβ and ROCK. Moreover, ROCK activation promotes the formation of neurofibrillary tangles and abnormal synaptic contraction. Additionally, ROCK activation can promote the neuroinflammatory response by activating microglia and astrocytes to release inflammatory cytokines. Therefore, ROCK is a promising drug target in AD; further, there is a need to elucidate the specific mechanism of action.

Keywords: Alzheimer’s disease; Amyloid-β; Neuroinflammation; Rho kinase; Tau.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Humans
  • Neuroinflammatory Diseases / metabolism*
  • rho-Associated Kinases / metabolism*
  • rhoA GTP-Binding Protein / metabolism*
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • MAPT protein, human
  • tau Proteins
  • RHOA protein, human
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein