title: Regulating the ubiquitin/proteasome pathway via cAMP-signaling: neuroprotective potential.
abstract: The cAMP-signaling pathway has been under intensive investigation for decades. It is a wonder that such a small simple molecule like cAMP can modulate a vast number of diverse processes in different types of cells. The ubiquitous involvement of cAMP-signaling in a variety of cellular events requires tight spatial and temporal control of its generation, propagation, compartmentalization, and elimination. Among the various steps of the cAMP-signaling pathway, G-protein-coupled receptors, adenylate cyclases, phosphodiesterases, the two major cAMP targets, i.e., protein kinase A and exchange protein activated by cAMP, as well as the A-kinase anchoring proteins, are potential targets for drug development. Herein we review the recent progress on the regulation and manipulation of different steps of the cAMP-signaling pathway. We end by focusing on the emerging role of cAMP-signaling in modulating protein degradation via the ubiquitin/proteasome pathway. New discoveries on the regulation of the ubiquitin/proteasome pathway by cAMP-signaling support the development of new therapeutic approaches to prevent proteotoxicity in chronic neurodegenerative disorders and other human disease conditions associated with impaired protein turnover by the ubiquitin/proteasome pathway and the accumulation of ubiquitin-protein aggregates.
authors.affiliation: Department of Biological Sciences, Hunter College and Graduate Center, City University of New York, 695 Park Avenue, New York, NY 10065, USA.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.forename: Maria E
authors.initials: ME
authors.lastname: Figueiredo-Pereira
mesh_terms: D005576:Colforsin / Q000627:therapeutic use; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000628:therapy; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D010726:Phosphodiesterase Inhibitors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D025801:Ubiquitin; D014665:Vasodilator Agents; D005576:Colforsin; D000242:Cyclic AMP; D046988:Proteasome Endopeptidase Complex