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

Donatella Pastore, Francesca Pacifici, Kunjan R. Dave, Raffaele Palmirotta, Alfonso Bellia, Guido Pasquantonio, Fiorella Guadagni, Giulia Donadel, Nicola Di Daniele, Pasquale Abete, Davide Lauro, Tatjana Rundek, Miguel A. Perez-Pinzon, David Della-Morte

Research output: Contribution to journalReview article

Abstract

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 ε, δ, and γPKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of εPKC, such as εReceptor for Activated C-Kinase (εRACK) 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 εPKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of γPKC and 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.

Original languageEnglish (US)
Article number3544
JournalInternational journal of molecular sciences
Volume20
Issue number14
DOIs
StatePublished - Jul 2 2019

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Keywords

  • aging
  • Alzheimer’s Diseases
  • brain
  • cerebrovascular disease
  • ischemic preconditioning
  • modulators
  • neurodegenerative diseases
  • pharmacogenetics
  • protein kinase c

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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