TY - JOUR
T1 - Age-Dependent Levels of Protein Kinase Cs in Brain
T2 - Reduction of Endogenous Mechanisms of Neuroprotection
AU - Pastore, Donatella
AU - Pacifici, Francesca
AU - Dave, Kunjan R.
AU - Palmirotta, Raffaele
AU - Bellia, Alfonso
AU - Pasquantonio, Guido
AU - Guadagni, Fiorella
AU - Donadel, Giulia
AU - Di Daniele, Nicola
AU - Abete, Pasquale
AU - Lauro, Davide
AU - Rundek, Tatjana
AU - Perez-Pinzon, Miguel A.
AU - Della-Morte, David
N1 - Funding Information:
Funding: This review was funded by following Institutes and Grants: The Evelyn F. McKnight Brain Institute of the Department of Neurology, University of Miami, Miami, FL; European Social Fund, under the Italian Ministry of Education, University and Research (PNR 2015-2020 ARS01_01163 PerMedNet – CUP B66G18000220005; National Institute of Neurologic Disorders and Stroke grants: R37 NS29993, R01 NS047655, and K24 NS062737; Fondazione Roma NCDS-2013-00000331 - Sarcopenia and Insulin Resistance in the Elderly; Age-Associated Inflammation as a Shared Pathogenic Mechanism and Potential Therapeutic Target; Fondazione Roma - Diabetes Mellitus, Regenerative and Reparative Processes, and Improvement of Pancreatic Beta Cell Function: Role of Bone Marrow-Mesenchymal Stem Cells, MicroRNAs, M2 Macrophages and Myeloid Derived Suppressor Cells.
Publisher Copyright:
© 2019 by the authors. All rights reserved.
PY - 2019/7/2
Y1 - 2019/7/2
N2 - 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.
AB - 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.
KW - Alzheimer’s Diseases
KW - aging
KW - brain
KW - cerebrovascular disease
KW - ischemic preconditioning
KW - modulators
KW - neurodegenerative diseases
KW - pharmacogenetics
KW - protein kinase c
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U2 - 10.3390/ijms20143544
DO - 10.3390/ijms20143544
M3 - Review article
C2 - 31331067
AN - SCOPUS:85071881751
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 14
M1 - 3544
ER -