Role of RhoA/ROCK signaling in Alzheimer's disease

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 beta-secretase activity and promotes amyloid-beta (A beta) production; moreover, A beta further activates ROCK. This is suggestive of a possible positive feedback role for A beta 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.

Automated summary

ROCK activation can promote the occurrence of Alzheimer's disease and may involve a positive feedback loop between Aβ and ROCK. Additionally, ROCK can also promote the formation of neurofibrillary tangles and exacerbate neuroinflammatory responses.