title: Activation of protein kinase C isozymes for the treatment of dementias.
abstract: Memories are much more easily impaired than improved. Dementias, a lasting impairment of memory function, occur in a variety of cognitive disorders and become more clinically dominant as the population ages. Protein kinase C is one of the "cognitive kinases," and plays an essential role in both memory acquisition and maintenance. Deficits in protein kinase C (PKC) signal cascades in neurons represent one of the earliest changes in the brains of patients with Alzheimer's disease (AD) and other types of memory impairment, including those related to cerebral ischemia and ischemic stroke. Inhibition or impairment of PKC activity results in compromised learning and memory, whereas an appropriate activation of certain PKC isozymes leads to an enhancement of learning and memory and/or antidementic effects. In preclinical studies, PKC activators have been shown to increase the expression and activity of PKC isozymes, thereby restoring PKC signaling and downstream activity, including stimulation of neurotrophic activity, synaptic/structural remodeling, and synaptogenesis in the hippocampus and related cortical areas. PKC activators also reduce the accumulation of neurotoxic amyloid and tau protein hyperphosphorylation and support anti-apoptotic processes in the brain. These observations strongly suggest that PKC pharmacology may represent an attractive area for the development of effective cognition-enhancing therapeutics for the treatment of dementias.
authors: Blanchette Rockefeller Neurosciences Institute, Morgantown, WV, USA.
authors: Miao-Kun
authors: MK
authors: Sun
authors: Daniel L
authors: DL
authors: Alkon
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D000818:Animals; D003704:Dementia / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008568:Memory; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C