Rho-associated protein kinases as therapeutic targets for both vascular and parenchymal pathologies in Alzheimer's disease.

The causes of late-onset Alzheimer's disease are unclear and likely multifactorial. Rho-associated protein kinases (ROCKs) are ubiquitously expressed signaling messengers that mediate a wide array of cellular processes. Interestingly, they play an important role in several vascular and brain pathologies implicated in Alzheimer's etiology, including hypertension, hypercholesterolemia, blood-brain barrier disruption, oxidative stress, deposition of vascular and parenchymal amyloid-beta peptides, tau hyperphosphorylation, and cognitive decline. The current review summarizes the functions of ROCKs with respect to the various risk factors and pathologies on both sides of the blood-brain barrier and present support for targeting ROCK signaling as a multifactorial and multi-effect approach for the prevention and amelioration of late-onset Alzheimer's disease. This article is part of the Special Issue "Vascular Dementia".