Role of protein kinase C delta in dopaminergic neurotoxic events

Abstract

The pro-apoptotic role of Protein kinase C delta (PKC delta), a member of the novel PKC subfamily, has been well documented in various pathological conditions. In the central nervous system, the possible role of PKC delta has been studied, mainly in the condition of dopaminergic loss. It has been suggested that the phosphorylation of PKC delta at tyrosine 311 residue (Tyr(311)) by redox-sensitive Src family kinases (SFKs) is critical for the caspase-3-mediated proteolytic cleavage, which produces the constitutively active cleaved form of PKC delta. Mitochondrial translocation of cleaved PKC delta has been suggested to facilitate mitochondria-derived apoptosis and oxidative burdens. Moreover, it has been suggested that PKC delta contribute to neuroinflammation through the transformation of microglia into the pro-inflammatory M1 phenotype and the assembly of membrane NADPH oxidase in dopaminergic impairments. Interestingly, mitochondrial respiratory chain inhibitors or neuroinflammogens have shown to induce PKC delta activation in dopaminergic systems. Thus, PKC delta activation may be one of the pivotal causes of neuropathologic events, and could amplify these processes further in a positive feedback manner. Furthermore, PKC delta may play an intermediary role in connecting each neuropathologic event. This review affords insight into the role of PKC delta in various dopaminergic neurotoxic models, which could provide a potential target for mitigating dopaminergic neurotoxicity.