Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?

Neuronal Signal. 2021 Oct 8;5(4):NS20210036. doi: 10.1042/NS20210036. eCollection 2021 Dec.

Abstract

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.

Keywords: Alzheimer's Disease; Enzyme mutation; Signal transduction; Spinocerebellar ataxia; neurodegeneration; protein kinase C.

Publication types

  • Review