Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis.

Abstract:

:Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. Many factors that inhibit cell death have been identified, but the mechanisms involved are not always fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neuroprotective activities during development. PACAP also inhibits apoptosis in cardiomyopathy, decreases glutamate-induced retinal injury, reduces neuronal loss in case of stroke, and prevents ethanol neurotoxicity. Most of the antiapoptotic effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression which inhibits cytochrome c release and blocks in turn caspase activation. PACAP also acts through the PI3K/Akt pathway and inhibits the expression of proapoptotic factors such as c-Jun or Bax. The remarkable effect of PACAP on the apoptotic cascade suggests that innovative PACAP derivatives could potentially be useful for treatment of post-traumatic lesions, chronic neurodegenerative diseases, cardiac ischemia and/or retinopathy.

journal_name

Curr Pharm Des

authors

Seaborn T,Masmoudi-Kouli O,Fournier A,Vaudry H,Vaudry D

doi

10.2174/138161211795049679

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

204-14

issue

3

eissn

1381-6128

issn

1873-4286

pii

BSP/CPD/E-Pub/000315

journal_volume

17

pub_type

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