AUTHOR=Hu Yong-Bo , Zou Yang , Huang Yue , Zhang Yong-Fang , Lourenco Guinevere F. , Chen Sheng-Di , Halliday Glenda M. , Wang Gang , Ren Ru-Jing TITLE=ROCK1 Is Associated with Alzheimer’s Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic Aβ Clearance JOURNAL=Frontiers in Cellular Neuroscience VOLUME=Volume 10 - 2016 YEAR=2016 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2016.00253 DOI=10.3389/fncel.2016.00253 ISSN=1662-5102 ABSTRACT=

Alzheimer’s disease (AD) is the most prevalent form of late-life dementia in the population, characterized by amyloid plaque formation and increased tau deposition, which is modulated by Rho-associated coiled-coil kinase 1 (ROCK1). In this study, we further analyze whether ROCK1 regulates the metabolism of amyloid precursor protein (APP). We show that ROCK1 is colocalized with mature amyloid-β (Aβ) plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aβ in a cell model of AD (confirmed by increased ROCK1 and decreased Beclin 1 protein levels, with neuronal autophagosome accumulation in prefrontal cortex of AD APP/PS1 mouse model). In vitro over-expression of ROCK1 leads to a decrease in Aβ secretion and an increase in the expression of autophagy-related molecules. ROCK1 interacts with Beclin1, an autophagy initiator, and enhances the intracellular accumulation of Aβ. Reciprocally, overexpression of APP/Aβ promotes ROCK1 expression. Our data suggest ROCK1 participates in regulating Aβ secretion, APP shedding and autophagosome accumulation, and that ROCK1, rather than other kinases, is more likely to be a targetable enzyme for AD therapy.