title: Effect of the pituitary adenylate cyclase-activating polypeptide on the autophagic activation observed in in vitro and in vivo models of Parkinson's disease.
abstract: 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.
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7; INSERM-U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, IRIB, Université de Rouen, 76821, Mont-Saint-Aignan, France; Laboratoire Samuel-de-Champlain, Université de Rouen, France/INRS, Canada.
authors.forename: Asma
authors.initials: A
authors.lastname: Lamine-Ajili
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Fahmy
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7; Laboratoire Samuel-de-Champlain, Université de Rouen, France/INRS, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Létourneau
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7.
authors.forename: David
authors.initials: D
authors.lastname: Chatenet
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7.
authors.forename: Patrick
authors.initials: P
authors.lastname: Labonté
authors.affiliation: INSERM-U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, IRIB, Université de Rouen, 76821, Mont-Saint-Aignan, France; Laboratoire Samuel-de-Champlain, Université de Rouen, France/INRS, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: INRS, Institut Armand-Frappier, 531 boul. des Prairies, Laval, QC, Canada H7V 1B7; Laboratoire Samuel-de-Champlain, Université de Rouen, France/INRS, Canada. Electronic address: alain.fournier@iaf.inrs.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D059290:Dopaminergic Neurons / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D006801:Humans; D020267:MPTP Poisoning / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008636:Mesencephalon / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*
chemical_list: C495402:Adcyap1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
keywords: Autophagy; Dopaminergic neuron survival; Mitochondrial functions; Neurodegeneration; PACAP; SH-SY5Y neuroblastoma cell survival