Protein kinase C activators as synaptogenic and memory therapeutics.
The last decade has witnessed a rapid progress in understanding of the molecular cascades that may underlie memory and memory disorders. Among the critical players, activity of protein kinase C (PKC) isoforms is essential for many types of learning and memory and their dysfunction, and is critical in memory disorders. PKC inhibition and functional deficits lead to an impairment of various types of learning and memory, consistent with the observations that neurotoxic amyloid inhibits PKC activity and that transgenic animal models with PKCbeta deficit exhibit impaired capacity in cognition. In addition, PKC isozymes play a regulatory role in amyloid production and accumulation. Restoration of the impaired PKC signal pathway pharmacologically results in an enhanced memory capacity and synaptic remodeling / repair and synaptogenesis, and, therefore, represents a potentially important strategy for the treatment of memory disorders, including Alzheimer's dementia. The PKC activators, especially those that are isozyme-specific, are a new class of drug candidates that may be developed as future memory therapeutics.
Sun
Miao-Kun
MK
Blanchette Rockefeller Neurosciences Institute, Rockville, MD 20850, USA. mksun@brni-jhu.org
Alkon
Daniel L
DL
D000818:Animals; D016503:Drug Delivery Systems; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011493:Protein Kinase C