Effect of the pituitary adenylate cyclase-activating polypeptide on the autophagic activation observed in in vitro and in vivo models of Parkinson's disease

Lamine-Ajili, Asma; Fahmy, Ahmed Mohamed; Létourneau, Myriam; Chatenet, David; Labonté, Patrick; Vaudry, David et Fournier, Alain (2016). Effect of the pituitary adenylate cyclase-activating polypeptide on the autophagic activation observed in in vitro and in vivo models of Parkinson's disease Biochimica et Biophysica Acta - Molecular Basis of Disease , vol. 1862 , nº 4. pp. 688-695. DOI: 10.1016/j.bbadis.2016.01.005.

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Résumé

Parkinson's disease (PD) is a neurodegenerative disorder that leads to destruction of the midbrain dopaminergic (DA) neurons. This phenomenon is related to apoptosis and its activation can be blocked by the pituitary adenylate cyclase-activating polypeptide (PACAP). Growing evidence indicates that autophagy, a self-degradation activity that cleans up the cell, is induced during the course of neurodegenerative diseases. However, the role of autophagy in the pathogenesis of neuronal disorders is yet poorly understood and the potential ability of PACAP to modulate the related autophagic activation has never been significantly investigated. Hence, we explored the putative autophagy-modulating properties of PACAP in in vitro and in vivo models of PD, using the neurotoxic agents 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), respectively, to trigger alterations of DA neurons. In both models, following the toxin exposure, PACAP reduced the autophagic activity as evaluated by the production of LC3 II, the modulation of the p62 protein levels, and the formation of autophagic vacuoles. The ability of PACAP to inhibit autophagy was also observed in an in vitro cell assay by the blocking of the p62-sequestration activity produced with the autophagy inducer rapamycin. Thus, the results demonstrated that autophagy is induced in PD experimental models and that PACAP exhibits not only anti-apoptotic but also anti-autophagic properties. © 2016 Elsevier B.V.

Type de document:	Article
Mots-clés libres:	Autophagy; Dopaminergic neuron survival; Mitochondrial; functions Neurodegeneration; PACAP; SH-SY5Y neuroblastoma cell survival
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	09 mai 2017 20:44
Dernière modification:	26 nov. 2020 16:39
URI:	https://espace.inrs.ca/id/eprint/4606

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