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 language | English (US) |
|---|---|
| Article number | 3544 |
| Journal | International journal of molecular sciences |
| Volume | 20 |
| Issue number | 14 |
| DOIs | |
| State | Published - 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
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 A.; Della-Morte, David.
In: International journal of molecular sciences, Vol. 20, No. 14, 3544, 02.07.2019.Research output: Contribution to journal › Review article
}
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
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
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 -