Adenylyl cyclase isoforms as novel therapeutic targets: an exciting example of excitotoxicity neuroprotection.
The use of transgenic animals lacking one or multiple adenylyl cyclase (AC) isoforms has provided significant information on the roles of AC-dependent signaling in the central nervous system. A recent study provides evidence that AC type 1 (AC1) might be important in glutamate-induced neuronal toxicity. However, the absolute AC specificity revealed in this study contrasts earlier work examining other forms of neurodegeneration. Nonetheless, these observations suggest that specific AC isoforms may represent novel targets for the treatment of central nervous system disorders. It is anticipated that such findings will help catalyze new drug discovery efforts to identify small-molecule modulators of individual AC isoforms.
Watts
Val J
VJ
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. wattsv@pharmacy.purdue.edu
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D016202:N-Methylaspartate / Q000633:toxicity; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D007527:Isoenzymes; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D000262:Adenylyl Cyclases