Protein kinase C isozymes: memory therapeutic potential.
PKC plays an important role in many types of learning and memory. Evidence has been provided that PKC activation and translocation are induced in associative learning tasks. PKC inhibition, on the other hand, impairs learning and memory, consistent with the observations that transgenic animal models with a particular PKC isoform deficit exhibit impaired capacity in cognition. The dramatic impact of PKC pharmacology on learning and memory is further emphasized by a regulatory role of PKC isozymes in amyloid production and accumulation. Recent study reveals that PKC activation greatly reduces neurotoxic amyloid production and accumulation. PKC activators, therefore, may have important therapeutic values in the treatment of dementia, especially when fine-tuning of selective isoform activity can be effectively achieved pharmacologically, with further development of isozymes-specific agents. The success of antidementia therapy with agents that act on PKC signaling cascades depends on whether such agents at their effective doses would significantly disrupt or interfere with other vital functions that rely on a narrow range of PKC activities.
Sun
Miao-Kun
MK
Blanchette Rockefeller Neurosciences Institute, West Virginia University, USA. mksun@brni-jhu.org
Alkon
Daniel L
DL
D000818:Animals; D030801:Animals, Genetically Modified; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007527:Isoenzymes; D007858:Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000201:enzymology*; D011493:Protein Kinase C / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007527:Isoenzymes; D011956:Receptors, Cell Surface; D011493:Protein Kinase C