Lordén Gema, Newton Alexandra C
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92037, U.S.A.
Neuronal Signal. 2021 Oct 8;5(4):NS20210036. doi: 10.1042/NS20210036. eCollection 2021 Dec.
Protein Kinase C (PKC) isozymes are tightly regulated kinases that transduce a myriad of signals from receptor-mediated hydrolysis of membrane phospholipids. They play an important role in brain physiology, and dysregulation of PKC activity is associated with neurodegeneration. Gain-of-function mutations in PKCα are associated with Alzheimer's disease (AD) and mutations in PKCγ cause spinocerebellar ataxia (SCA) type 14 (SCA14). This article presents an overview of the role of the conventional PKCα and PKCγ in neurodegeneration and proposes repurposing PKC inhibitors, which failed in clinical trials for cancer, for the treatment of neurodegenerative diseases.
蛋白激酶C(PKC)同工酶是受到严格调控的激酶,可转导来自受体介导的膜磷脂水解产生的大量信号。它们在脑生理学中发挥重要作用,PKC活性失调与神经退行性变有关。PKCα的功能获得性突变与阿尔茨海默病(AD)相关,而PKCγ的突变会导致14型脊髓小脑共济失调(SCA14)。本文概述了传统型PKCα和PKCγ在神经退行性变中的作用,并提议重新利用在癌症临床试验中失败的PKC抑制剂来治疗神经退行性疾病。