{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:46:17Z","timestamp":1773211577118,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero Italiano della Salute","award":["RC201802P004271 and RC2019.1.4_MANCO1.5."],"award-info":[{"award-number":["RC201802P004271 and RC2019.1.4_MANCO1.5."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Post-translational modulation of peptidylprolyl isomerase Pin1 might link impaired glucose metabolism and neurodegeneration, being Pin1 effectors target for the glucagon-Like-Peptide1 analog liraglutide. We tested the hypotheses in Pin1 silenced cells (SH-SY5Y) treated with 2-deoxy-d-glucose (2DG) and methylglyoxal (MG), stressors causing altered glucose trafficking, glucotoxicity and protein glycation. Rescue by liraglutide was investigated. Pin1 silencing caused increased levels of reactive oxygen species, upregulated energy metabolism as suggested by raised levels of total ATP content and mRNA of SIRT1, PGC1\u03b1, NRF1; enhanced mitochondrial fission events as supported by raised protein expression of FIS1 and DRP1. 2DG and MG reduced significantly cell viability in all the cell lines. In Pin1 KD clones, 2DG exacerbated altered mitochondrial dynamics causing higher rate of fission events. Liraglutide influenced insulin signaling pathway (GSK3b\/Akt); improved cell viability also in cells treated with 2DG; but it did not revert mitochondrial dysfunction in Pin1 KD model. In cells treated with MG, liraglutide enhanced cell viability, reduced ROS levels and cell death (AnnexinV\/PI); and trended to reduce anti-apoptotic signals (BAX, BCL2, CASP3). Pin1 silencing mimics neuronal metabolic impairment of patients with impaired glucose metabolism and neurodegeneration. Liraglutide rescues to some extent cellular dysfunctions induced by Pin1 silencing.<\/jats:p>","DOI":"10.3390\/ijms20205064","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T03:54:13Z","timestamp":1571025253000},"page":"5064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Liraglutide Treatment Ameliorates Neurotoxicity Induced by Stable Silencing of Pin1"],"prefix":"10.3390","volume":"20","author":[{"given":"Marzia","family":"Bianchi","sequence":"first","affiliation":[{"name":"Research Area for Multi-factorial Diseases, Obesity and Diabetes, Bambino Ges\u00f9 Children\u2019s Research Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"D\u2019Oria","sequence":"additional","affiliation":[{"name":"Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesu\u2019 Children\u2019s Research Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rita","family":"Braghini","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Complex Phenotypes Research Unit, Bambino Ges\u00f9 Children\u2019s Research Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-0003","authenticated-orcid":false,"given":"Stefania","family":"Petrini","sequence":"additional","affiliation":[{"name":"Confocal Microscopy Core Facility, Research Laboratories, Bambino Gesu\u2019 Children\u2019s Research Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-975X","authenticated-orcid":false,"given":"Melania","family":"Manco","sequence":"additional","affiliation":[{"name":"Research Area for Multi-factorial Diseases, Obesity and Diabetes, Bambino Ges\u00f9 Children\u2019s Research Hospital, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), viale di San Paolo 15, 00146 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bianchi, M., and Manco, M. 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