Adenylyl cyclase signalling complexes - Pharmacological challenges and opportunities
Michelle L Halls1, Dermot M F Cooper2
1Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, Victoria, Australia.
Pharmacology & Therapeutics
|January 31, 2017
Summary
Cyclic adenosine monophosphate (cAMP) signaling is crucial for physiology but challenging to inhibit due to complex regulation and conserved enzyme structures. New strategies are needed to specifically target adenylyl cyclase functions in disease.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Signaling
Background:
- Cyclic adenosine monophosphate (cAMP) is a vital second messenger regulating numerous physiological processes.
- cAMP signaling is tightly controlled by phosphorylation, protein scaffolding, and subcellular compartmentalization.
- Nine membrane-bound adenylyl cyclases (ACs) generate cAMP, but their conserved catalytic sites complicate direct inhibition.
Purpose of the Study:
- To review the biochemistry and cell biology of membrane-bound adenylyl cyclases.
- To discuss the nature of cAMP signals produced by adenylyl cyclases.
- To evaluate strategies for targeting cAMP signaling, addressing limitations of direct AC inhibition.
Main Methods:
- Literature review of adenylyl cyclase biochemistry and cell biology.
- Analysis of cAMP signaling pathway regulation.
- Evaluation of therapeutic targeting strategies for adenylyl cyclases.
Main Results:
- Membrane-bound adenylyl cyclases exhibit complex activation and organization.
- Direct inhibition of adenylyl cyclase activity faces significant challenges.
- Alternative strategies offer potential for specific targeting of adenylyl cyclase signaling.
Conclusions:
- Understanding adenylyl cyclase complexity is key to developing targeted therapies.
- The intricate regulation of adenylyl cyclases presents opportunities for selective disease intervention.
- Targeting discrete adenylyl cyclase functions may offer novel therapeutic approaches for various diseases.
Keywords:
Adenylyl cyclaseAdenylyl cyclase inhibitionCalciumCompartmentalisationProtein complexescAMPMore Related Videos
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