Age-related alteration of PKC, a key enzyme in memory processes: physiological and pathological examples.
Brain aging is characterized by a progressive decline of the cognitive and memory functions. It is becoming increasingly clear that protein phosphorylation and, in particular, the activity of the calcium-phospholipid-dependent protein kinase C (PKC) may be one of the fundamental cellular changes associated with memory function. PKC is a multigene family of enzymes highly expressed in brain tissues. The activation of kinase C is coupled with its translocation from the cytosol to different intracellular sites and recent studies have demonstrated the key role played by several anchoring proteins in this mechanism. PKC-phosphorylating activity appears to be impaired during senescence at brain level in a strain-dependent fashion in rodents. Whereas the levels of the various isoforms do not show age-related alterations, the enzyme translocation upon phorbol-ester treatment is deficitary among all strains investigated. Anchoring proteins may contribute to this activation deficit. We discuss also modifications of the PKC system in Alzheimer's disease that may be related to pathological alterations in neurotransmission. A better insight of the different factors controlling brain-PKC activation may be important not only for elucidating the molecular basis of neuronal transmission, but also for identifying new approaches for correcting or even preventing age-dependent changes in brain function.
Pascale
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A
Institute of Pharmacol. Sciences, University of Milano, Italy.
Govoni
S
S
Battaini
F
F
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D001921:Brain / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008568:Memory / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction
D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D011493:Protein Kinase C