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-phosph olipid-dependent protein kinase C (PKC) may be one of the fundamental cellular changes associated with memory function. PKC is a multigene f amily of enzymes highly expressed in brain tissues. The activation of kinase C is coupled with its translocation from the cytosol to differe nt intracellular sites and recent studies have demonstrated the key ro le played by several anchoring proteins in this mechanism. PKC-phospho rylating activity appears to be impaired during senescence at brain le vel in a strain-dependent fashion in rodents, Whereas the levels of th e various isoforms do not show age-related alterations, the enzyme tra nslocation upon phorbol-ester treatment is deficitary among all strain s investigated. Anchoring proteins may contribute to this activation d eficit. We discuss also modifications of the PKC system in Alzheimer's disease that may be related to pathological alterations in neurotrans mission. A better insight of the different factors controlling brain-P KC activation may be important not only for elucidating the molecular basis of neuronal transmission, but also for identifying new approache s for correcting or even preventing age-dependent changes in brain fun ction.