Bryostatin-1: pharmacology and therapeutic potential as a CNS drug.
Bryostatin-1 is a powerful protein kinase C (PKC) agonist, activating PKC isozymes at nanomolar concentrations. Pharmacological studies of bryostatin-1 have mainly been focused on its action in preventing tumor growth. Emerging evidence suggests, however, that bryostatin-1 exhibits additional important pharmacological activities. In preclinical studies bryostatin-1 has been shown at appropriate doses to have cognitive restorative and antidepressant effects. The underlying pharmacological mechanisms may involve an activation of PKC isozymes, induction of synthesis of proteins required for long-term memory, restoration of stress-evoked inhibition of PKC activity, and reduction of neurotoxic amyloid accumulation and tau protein hyperphosphorylation. The therapeutic potential of bryostatin-1 as a CNS drug should be further explored.
Sun
Miao-Kun
MK
Blanchette Rockefeller Neurosciences Institute, Rockville, MD 20850, USA. mksun@brni-jhu.org
Alkon
Daniel L
DL
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D054713:Bryostatins; D002490:Central Nervous System / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011493:Protein Kinase C / Q000378:metabolism
D000970:Antineoplastic Agents; D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C