Akt in the pathogenesis of COPD.
In this review we consider the therapeutic potential of targeting Akt for the treatment of COPD. Akt is a serine/threonine protein kinase that functions as a signaling intermediate linked to multiple signaling programs involved in survival, inflammation, and growth. Akt is closely associated with key membrane-bound receptors and represents a convergent integration point for multiple stimuli implicated in COPD pathogenesis. Persistent activation of Akt secondary to somatic mutations in regulatory oncogenes, such as PTEN, may explain why inflammation in COPD does not resolve when smoking is ceased. Akt is also implicated in the systemic manifestations of COPD such as skeletal muscle wasting and metabolic disturbances. Furthermore, targeting Akt may provide a useful means of limiting the severity and duration of disease exacerbations in COPD. As such, Akt represents a particularly attractive therapeutic target for the treatment of COPD. Interestingly, current knowledge suggests that both inhibitors and activators of Akt may be useful for treating different clinical subpopulations of COPD patients.
The Lung Disease Research Laboratories, Cooperative Research Centre for Chronic Inflammatory Diseases, Department of Pharmacology, The University of Melbourne, VIC, Australia. bozis@unimelb.edu.au
Steven
S
Bozinovski
Ross
R
Vlahos
Michelle
M
Hansen
Ken
K
Liu
Gary P
GP
Anderson
D017209:Apoptosis; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology
D017346:Protein Serine-Threonine Kinases