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ROCK1 Is Associated with Alzheimer's Disease-Specific Plaques, as well as Enhances Autophagosome Formation But not Autophagic Aß Clearance.
Hu, Yong-Bo; Zou, Yang; Huang, Yue; Zhang, Yong-Fang; Lourenco, Guinevere F; Chen, Sheng-Di; Halliday, Glenda M; Wang, Gang; Ren, Ru-Jing.
Afiliação
  • Hu YB; Department of Neurology and Neuroscience Institute, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.
  • Zou Y; Department of Neurology and Neuroscience Institute, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.
  • Huang Y; Neuroscience Research Australia and Faculty of Medicine, University of New South Wales (UNSW) Sydney, NSW, Australia.
  • Zhang YF; Research Laboratory of Cell Regulation, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
  • Lourenco GF; Neuroscience Research Australia and Faculty of Medicine, University of New South Wales (UNSW) Sydney, NSW, Australia.
  • Chen SD; Department of Neurology and Neuroscience Institute, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.
  • Halliday GM; Neuroscience Research Australia and Faculty of Medicine, University of New South Wales (UNSW) Sydney, NSW, Australia.
  • Wang G; Department of Neurology and Neuroscience Institute, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.
  • Ren RJ; Department of Neurology and Neuroscience Institute, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai, China.
Front Cell Neurosci ; 10: 253, 2016.
Article em En | MEDLINE | ID: mdl-27853422
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-ß (Aß) plaques in patients with AD, in that ROCK1 enhances the amyloidogenic pathway, and that ROCK1 mediated autophagy enhances the intracellular buildup of Aß 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 Aß secretion and an increase in the expression of autophagy-related molecules. ROCK1 interacts with Beclin1, an autophagy initiator, and enhances the intracellular accumulation of Aß. Reciprocally, overexpression of APP/Aß promotes ROCK1 expression. Our data suggest ROCK1 participates in regulating Aß secretion, APP shedding and autophagosome accumulation, and that ROCK1, rather than other kinases, is more likely to be a targetable enzyme for AD therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Risk_factors_studies Idioma: En Ano de publicação: 2016 Tipo de documento: Article