Regulating the Ubiquitin/Proteasome Pathway Via cAMP-signaling: Neuroprotective Potential

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• 作者：He Huang (1)
  Hu Wang (1)
  Maria E. Figueiredo-Pereira (1)
  
• 关键词：Ubiquitin/proteasome pathway ; cAMP ; Therapy ; Protein aggregation
• 刊名：Cell Biochemistry and Biophysics
• 出版年：2013
• 出版时间：September 2013
• 年：2013
• 卷：67
• 期：1
• 页码：55-66
• 全文大小：314KB
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• 作者单位：He Huang (1)
  Hu Wang (1)
  Maria E. Figueiredo-Pereira (1)
  
  1. Department of Biological Sciences, Hunter College and Graduate Center, City University of New York, 695 Park Avenue, New York, NY, 10065, USA
  

文摘

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.