Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection

Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer's Disease (AD) and cerebral ischemia. Specifically epsilon, delta, and gamma PKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of epsilon PKC, such as psi epsilon Receptor for Activated C-Kinase (psi epsilon RACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing epsilon PKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of delta PKC and gamma PKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.