Role of RhoA-ROCK signaling inhibitor fasudil in Alzheimer disease

Abstract

Alzheimer disease (AD) is the most common neurodegenerative brain disease linked with the development of dementia. AD neuropathology is characterized by the progressive accumulation of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Different signaling pathways are involved in AD neuropathology through modulation of Aβ formation and tau protein hyperphosphorylation. One of these signaling is Rho-associated protein kinase (ROCK). RhoA-ROCK signaling boosts the production of Aβ through activation of β-secretase and augments the formation of NFTs. RhoA-ROCK signaling is also intricate in the development of oxidative stress and neuroinflammation. Consequently, targeting RhoA-ROCK signaling by specific inhibitors, such as fasudil, may decrease AD neuropathology. Therefore, this perspective aims to discuss the role of RhoA-ROCK signaling in the pathogenesis of AD and how fasudil could be effective in its treatment.