Conventional protein kinase C in the brain: repurposing cancer drugs for neurodegenerative treatment?
Gema Lordén, Alexandra C. Newton
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.
Topics & Concepts
RepurposingNeurodegenerationProtein kinase CKinaseTransmembrane proteinProtein kinase AMedicineIsozymeCancer researchDiseaseDrug repositioningNeuroprotectionPharmacologyCancerBiologySpinocerebellar ataxiaCell biologyAtaxiaClinical trialMutationBioinformaticsSignal transductionNeuroscienceDrug discoveryMechanism of actionGeneChemistryASK1Membrane proteinEnzymeCancer cellProtein Kinase Regulation and GTPase SignalingPhosphodiesterase function and regulationAlzheimer's disease research and treatments