{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:55:07Z","timestamp":1789444507858,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,5,10]],"date-time":"2007-05-10T00:00:00Z","timestamp":1178755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parkinson's disease (PD) and 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP) toxicity are both associated with dopaminergic neuron death in the substantia nigra. Although a variety of evidence has shown that degenerative cells have apoptotic features, the role of apoptosis in disease pathology remains controversial. The 1\u2010methyl\u20104\u2010phenylpyridinium ion (MPP<jats:sup>+<\/jats:sup>), a metabolite of MPTP, was recently shown to alter the expression of proteins involved in translational control. The initiation step of translational control is regulated by a cascade of phosphorylation affecting proteins of the antiapoptotic way controlled by mammalian target of rapamycin (mTOR) and of the proapoptotic way controlled by double\u2010stranded RNA protein\u2013dependent kinase (PKR). A study showed that MPP<jats:sup>+<\/jats:sup>induced an increase in eIF2\u03b1 phosphorylation, leading to inhibition of protein synthesis. The aims of our study were: (1) to assess the effects of MPP<jats:sup>+<\/jats:sup>toxicity on molecular factors of PKR and mTOR signaling pathways in murine neuroblastoma cells, and (2) to examine the ability of VIP and PACAP peptides to counteract the MPP<jats:sup>+<\/jats:sup>toxicity. Our findings showed that MPP<jats:sup>+<\/jats:sup>induced phosphorylation of eIF2\u03b1 and significantly reduced the expression of phosphorylated mTOR, p70S6K, eIF4E, and 4E\u2010BP1, suggesting its toxicity in controlling protein synthesis. Furthermore, the VIP peptide had no effect on either the PKR or the mTOR signaling pathway. On the contrary, the PACAP 27 neuropeptide prevented MPP<jats:sup>+<\/jats:sup>\u2010induced eIF2\u03b1 phosphorylation and blocked MPP<jats:sup>+<\/jats:sup>toxicity in molecular factors of the mTOR pathway. And last, PACAP 27 seemed to protect Neuro\u20102a cells from the apoptotic process as assessed by the decreased nuclear condensation after DAPI staining. These results could open new paths of research of PACAP in PD. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.21318","type":"journal-article","created":{"date-parts":[[2007,5,10]],"date-time":"2007-05-10T22:52:03Z","timestamp":1178837523000},"page":"2017-2025","source":"Crossref","is-referenced-by-count":38,"title":["Neuroprotective effects of pituitary adenylate cyclase\u2013activating polypeptide (PACAP) in MPP<sup>+<\/sup>\u2010induced alteration of translational control in Neuro\u20102a neuroblastoma cells"],"prefix":"10.1002","volume":"85","author":[{"given":"Julie","family":"Deguil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jailloux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guyl\u00e8ne","family":"Page","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Fauconneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Houeto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Philippe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Marc","family":"Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Pain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,10]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"25","article-title":"Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease","volume":"12","author":"Anglade P","year":"1997","journal-title":"Histol Histopathol"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb19825.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.48.301"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2004.07.005"},{"key":"e_1_2_6_6_1","first-page":"95","article-title":"Dopamine and dopamine metabolites in Parkinson's disease \u2013a review","volume":"5","author":"Barbeau A","year":"1968","journal-title":"Proc Aust Assoc Neurol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.104.6.1603"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/335639a0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.01237.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200212200-00011"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(85)91071-X"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi178"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00986962"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2001.tb00157.x"},{"key":"e_1_2_6_15_1","first-page":"307","article-title":"Neuroprotective potential of three neuropeptides PACAP, VIP and PHI","volume":"57","author":"Dejda A","year":"2005","journal-title":"Pharmacol Rep"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10098"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0799fje"},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1016\/S0021-9258(18)42737-8","article-title":"The 38\u2010amino acid form of pituitary adenylate cyclase\u2010activating polypeptide stimulates dual signaling cascades in PC12 cells and promotes neurite outgrowth","volume":"267","author":"Deutsch PJ","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00642-6"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1999.4683"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.109.4.1467"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90888-E"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19990301)55:5<620::AID-JNR9>3.0.CO;2-S"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.913"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.912401"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-09889-9_6"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.9.5.923"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2002.809"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0031-6997(24)01360-7","article-title":"International Union of Pharmacology. 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