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 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

Fingerprint

Protein Kinases
brain
Brain
proteins
Proteins
Cerebrovascular Disorders
Ischemic Preconditioning
Neurodegenerative diseases
hippocampus
Modulators
Neurodegenerative Diseases
ischemia
modulators
preconditioning
Hippocampus
Neuroprotection
Resveratrol
Brain Ischemia
disabilities
mortality

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

Cite this

Age-Dependent Levels of Protein Kinase Cs in Brain : Reduction of Endogenous Mechanisms of Neuroprotection. / Pastore, Donatella; Pacifici, Francesca; Dave, Kunjan R; Palmirotta, Raffaele; Bellia, Alfonso; Pasquantonio, Guido; Guadagni, Fiorella; Donadel, Giulia; Di Daniele, Nicola; Abete, Pasquale; Lauro, Davide; Rundek, Tatjana; Perez-Pinzon, Miguel; Della Morte, David.

In: International journal of molecular sciences, Vol. 20, No. 14, 3544, 02.07.2019.

Research output: Contribution to journalReview article

Pastore, D, Pacifici, F, Dave, KR, Palmirotta, R, Bellia, A, Pasquantonio, G, Guadagni, F, Donadel, G, Di Daniele, N, Abete, P, Lauro, D, Rundek, T, Perez-Pinzon, M & Della Morte, D 2019, 'Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection', International journal of molecular sciences, vol. 20, no. 14, 3544. https://doi.org/10.3390/ijms20143544
Pastore, Donatella ; Pacifici, Francesca ; Dave, Kunjan R ; Palmirotta, Raffaele ; Bellia, Alfonso ; Pasquantonio, Guido ; Guadagni, Fiorella ; Donadel, Giulia ; Di Daniele, Nicola ; Abete, Pasquale ; Lauro, Davide ; Rundek, Tatjana ; Perez-Pinzon, Miguel ; Della Morte, David. / Age-Dependent Levels of Protein Kinase Cs in Brain : Reduction of Endogenous Mechanisms of Neuroprotection. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 14.
@article{fee27e0c5ee04eb3b5ed505ddfec2459,
title = "Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection",
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.",
keywords = "aging, Alzheimer’s Diseases, brain, cerebrovascular disease, ischemic preconditioning, modulators, neurodegenerative diseases, pharmacogenetics, protein kinase c",
author = "Donatella Pastore and Francesca Pacifici and Dave, {Kunjan R} and Raffaele Palmirotta and Alfonso Bellia and Guido Pasquantonio and Fiorella Guadagni and Giulia Donadel and {Di Daniele}, Nicola and Pasquale Abete and Davide Lauro and Tatjana Rundek and Miguel Perez-Pinzon and {Della Morte}, David",
year = "2019",
month = "7",
day = "2",
doi = "10.3390/ijms20143544",
language = "English (US)",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "14",

}

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

AU - Della Morte, David

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 - aging

KW - Alzheimer’s Diseases

KW - brain

KW - cerebrovascular disease

KW - ischemic preconditioning

KW - modulators

KW - neurodegenerative diseases

KW - pharmacogenetics

KW - protein kinase c

UR - http://www.scopus.com/inward/record.url?scp=85071881751&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071881751&partnerID=8YFLogxK

U2 - 10.3390/ijms20143544

DO - 10.3390/ijms20143544

M3 - Review article

VL - 20

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 14

M1 - 3544

ER -