{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:57:15Z","timestamp":1780606635457,"version":"3.54.1"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente, Ministry of Health, Italy","award":["2021\/FF Neuromed"],"award-info":[{"award-number":["2021\/FF Neuromed"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b1-Synuclein (\u03b1-syn) is a protein involved in neuronal degeneration. However, the family of synucleins has recently been demonstrated to be involved in the mechanisms of oncogenesis by selectively accelerating cellular processes leading to cancer. Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, with a specifically high neurotropism. The molecular bases of this biological behavior are currently poorly understood. Here, \u03b1-synuclein was analyzed concerning the protein expression in PDAC and the potential association with PDAC neurotropism. Tumor (PDAC) and extra-tumor (extra-PDAC) samples from 20 patients affected by PDAC following pancreatic resections were collected at the General Surgery Unit, University of Pisa. All patients were affected by moderately or poorly differentiated PDAC. The amount of \u03b1-syn was compared between tumor and extra-tumor specimen (sampled from non-affected neighboring pancreatic areas) by using in situ immuno-staining with peroxidase anti-\u03b1-syn immunohistochemistry, \u03b1-syn detection by using Western blotting, and electron microscopy by using \u03b1-syn-conjugated immuno-gold particles. All the methods consistently indicate that each PDAC sample possesses a higher amount of \u03b1-syn compared with extra-PDAC tissue. Moreover, the expression of \u03b1-syn was much higher in those PDAC samples from tumors with perineural infiltration compared with tumors without perineural infiltration.<\/jats:p>","DOI":"10.3390\/ijms23073775","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:44:52Z","timestamp":1648590292000},"page":"3775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In Pancreatic Adenocarcinoma Alpha-Synuclein Increases and Marks Peri-Neural Infiltration"],"prefix":"10.3390","volume":"23","author":[{"given":"Matteo","family":"Bianchini","sequence":"first","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8715-9465","authenticated-orcid":false,"given":"Maria","family":"Giambelluca","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-9393","authenticated-orcid":false,"given":"Maria Concetta","family":"Scavuzzo","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2156-369X","authenticated-orcid":false,"given":"Gregorio","family":"Di Franco","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Guadagni","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Palmeri","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7135-2666","authenticated-orcid":false,"given":"Niccol\u00f2","family":"Furbetta","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desir\u00e9e","family":"Gianardi","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Costa","sequence":"additional","affiliation":[{"name":"General Surgery Unit, ASL Toscana Nord Ovest Pontedera Hospital, 56025 Pontedera, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0366-9653","authenticated-orcid":false,"given":"Manuel","family":"Gentiluomo","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5220-5997","authenticated-orcid":false,"given":"Raffaele","family":"Gaeta","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Emanuele","family":"Pollina","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology, Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Falcone","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9307-2326","authenticated-orcid":false,"given":"Caterina","family":"Vivaldi","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Di Candio","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4889","authenticated-orcid":false,"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed-Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla Letizia","family":"Busceti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed-Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Soldani","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Puglisi-Allegra","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed-Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-9556","authenticated-orcid":false,"given":"Luca","family":"Morelli","sequence":"additional","affiliation":[{"name":"General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"},{"name":"EndoCAS (Center for Computer Assisted Surgery), University of Pisa, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-5084","authenticated-orcid":false,"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy"},{"name":"IRCCS Neuromed-Istituto Neurologico Mediterraneo, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s004390050792","article-title":"Identification, localization and characterization of the human \u03b3-synuclein gene","volume":"103","author":"Lavedan","year":"1998","journal-title":"Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1101\/gr.8.9.871","article-title":"The synuclein family","volume":"8","author":"Lavedan","year":"1998","journal-title":"Genome Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0166-2236(97)01213-7","article-title":"The synucleins: A family of proteins involved in synaptic function, plasticity, neurodegeneration and disease","volume":"21","author":"Clayton","year":"1998","journal-title":"Trends Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Barba, L., Paolini Paoletti, F., Bellomo, G., Gaetani, L., Halbgebauer, S., Oeckl, P., Otto, M., and Parnetti, L. (2022). Alpha and Beta Synucleins: From Pathophysiology to Clinical Application as Biomarkers. Mov. Disord.","DOI":"10.1002\/mds.28941"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a024091","DOI":"10.1101\/cshperspect.a024091","article-title":"Cell biology and pathophysiology of \u03b1-synuclein","volume":"8","author":"Sharma","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E4","DOI":"10.1038\/nature12125","article-title":"Properties of native brain \u03b1-synuclein","volume":"498","author":"Vivona","year":"2013","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"737195","DOI":"10.3389\/fneur.2021.737195","article-title":"The Concept of \u03b1-Synuclein Strains and How Different Conformations May Explain Distinct Neurodegenerative Disorders","volume":"12","author":"Malfertheiner","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with Lewy bodies","volume":"95","author":"Spillantini","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Upcott, M., Chaprov, K.D., and Buchman, V.L. (2021). Toward a Disease-Modifying Therapy of Alpha-Synucleinopathies: New Molecules and New Approaches Came into the Limelight. Molecules, 26.","DOI":"10.3390\/molecules26237351"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"736978","DOI":"10.3389\/fmed.2021.736978","article-title":"Alpha-Synuclein Aggregation in Parkinson\u2019s Disease","volume":"8","author":"Srinivasan","year":"2021","journal-title":"Front. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11282","DOI":"10.1073\/pnas.90.23.11282","article-title":"Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease","volume":"90","author":"Ueda","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/sj.mp.4000446","article-title":"Alpha synuclein is present in Lewy bodies in sporadic Parkinson\u2019s disease","volume":"3","author":"Mezey","year":"1998","journal-title":"Mol. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S0306-4522(03)00036-8","article-title":"Role of alpha-synuclein in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in mice","volume":"118","author":"Fornai","year":"2003","journal-title":"Neuroscience"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fan, T.-S., Liu, S.C.-H., and Wu, R.-M. (2021). Alpha-Synuclein and Cognitive Decline in Parkinson Disease. Life, 11.","DOI":"10.3390\/life11111239"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shan, F.Y., Fung, K.-M., Zieneldien, T., Kim, J., Cao, C., and Huang, J.H. (2021). Examining the Toxicity of \u03b1-Synuclein in Neurodegenerative Disorders. Life, 11.","DOI":"10.3390\/life11111126"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00423-016-1494-0","article-title":"Robotic assisted versus pure laparoscopic surgery of the adrenal glands: A case-control study comparing surgical techniques","volume":"401","author":"Morelli","year":"2016","journal-title":"Langenbeck\u2019s Arch. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s13578-021-00709-y","article-title":"\u03b1-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: The pathobiology of a paradox","volume":"11","author":"Simon","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1096\/fj.07-8379rev","article-title":"\u03b3-Synuclein and the progression of cancer","volume":"21","author":"Ahmad","year":"2007","journal-title":"FASEB J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1158\/0008-5472.CAN-05-1089","article-title":"Loss of epigenetic control of synuclein-\u03b3 gene as a molecular indicator of metastasis in a wide range of human cancers","volume":"65","author":"Liu","year":"2005","journal-title":"Cancer Res."},{"key":"ref_21","first-page":"742","article-title":"Stimulation of breast cancer invasion and metastasis by synuclein \u03b31","volume":"59","author":"Jia","year":"1999","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7593","DOI":"10.1038\/sj.onc.1206880","article-title":"Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1","volume":"22","author":"Gupta","year":"2003","journal-title":"Oncogene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10549-005-6938-0","article-title":"Synuclein gamma inhibits the mitotic checkpoint function and promotes chromosomal instability of breast cancer cells","volume":"94","author":"Inaba","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35050","DOI":"10.1074\/jbc.M201650200","article-title":"\u03b3-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways","volume":"277","author":"Pan","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1002\/mds.28655","article-title":"Linking Parkinson\u2019s Disease and Melanoma: Interplay Between \u03b1-Synuclein and Pmel17 Amyloid Formation","volume":"36","author":"Dean","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1038\/s41598-021-84443-y","article-title":"Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth","volume":"11","author":"Shekoohi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ejma, M., Madetko, N., Brzecka, A., Guranski, K., Alster, P., Misiuk-Hoj\u0142o, M., Somasundaram, S.G., Kirkland, C.E., and Aliev, G. (2020). The links between parkinson\u2019s disease and cancer. Biomedicines, 8.","DOI":"10.3390\/biomedicines8100416"},{"key":"ref_28","first-page":"5979","article-title":"Establishment and validation of an autophagy-related prognostic signature for survival predicting in cutaneous melanoma","volume":"11","author":"Fei","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e28553","DOI":"10.1097\/MD.0000000000028553","article-title":"The new horizon of biomarker in melanoma patients: A study based on autophagy-related long non-coding RNA","volume":"101","author":"Li","year":"2022","journal-title":"Medicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3322\/canjclin.57.1.43","article-title":"Cancer statistics","volume":"57","author":"Jemal","year":"2007","journal-title":"CA Cancer J. Clin."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJM199202133260706","article-title":"Pancreatic carcinoma","volume":"326","author":"Warshaw","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1056\/NEJMra0901557","article-title":"Pancreatic cancer","volume":"362","author":"Hidalgo","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_33","first-page":"294","article-title":"How Grim is Pancreatic Cancer?","volume":"10","author":"Weledji","year":"2016","journal-title":"Oncol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1097\/00006676-200305000-00002","article-title":"Neural invasion in the staging of pancreatic cancer","volume":"26","author":"Pour","year":"2003","journal-title":"Pancreas"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"668","DOI":"10.2214\/AJR.09.3285","article-title":"Pathways of extrapancreatic perineural invasion by pancreatic adenocarcinoma: Evaluation with 3D volume-rendered MDCT imaging","volume":"194","author":"Deshmukh","year":"2010","journal-title":"AJR. Am. J. Roentgenol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.suronc.2017.01.007","article-title":"The influence of neural invasion on survival and tumor recurrence in pancreatic ductal adenocarcinoma\u2014A systematic review and meta-analysis","volume":"26","author":"Schorn","year":"2017","journal-title":"Surg. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ctrv.2017.03.003","article-title":"The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma\u2014A systematic review and meta-analysis","volume":"55","author":"Schorn","year":"2017","journal-title":"Cancer Treat. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Crippa, S., Pergolini, I., Javed, A.A., Honselmann, K.C., Weiss, M.J., Di Salvo, F., Burkhart, R., Zamboni, G., Belfiori, G., and Ferrone, C.R. (2020). Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma. Ann. Surg., 33086324.","DOI":"10.1016\/j.pan.2019.05.154"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/cncr.20321","article-title":"Overexpression of synuclein-\u03b3 in pancreatic adenocarcinoma","volume":"101","author":"Li","year":"2004","journal-title":"Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Limanaqi, F., Biagioni, F., Busceti, C.L., Ryskalin, L., Polzella, M., Frati, A., and Fornai, F. (2019). Phytochemicals bridging autophagy induction and alpha-synuclein degradation in parkinsonism. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133274"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13046-021-02231-y","article-title":"Restriction of extracellular lipids renders pancreatic cancer dependent on autophagy","volume":"41","author":"Saliakoura","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"743938","DOI":"10.3389\/fimmu.2021.743938","article-title":"Identification of an Autophagy-Related Pair Signature for Predicting Prognoses and Immune Activity in Pancreatic Adenocarcinoma","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.pan.2020.08.004","article-title":"The occurrence of prion protein in surgically resected pancreatic adenocarcinoma","volume":"20","author":"Bianchini","year":"2020","journal-title":"Pancreatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7324","DOI":"10.3748\/wjg.v27.i42.7324","article-title":"Detailing the ultrastructure\u2019s increase of prion protein in pancreatic adenocarcinoma","volume":"27","author":"Bianchini","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ryskalin, L., Busceti, C.L., Biagioni, F., Limanaqi, F., Familiari, P., Frati, A., and Fornai, F. (2019). Prion protein in glioblastoma multiforme. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20205107"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ryskalin, L., Biagioni, F., Busceti, C.L., Giambelluca, M.A., Morelli, L., Frati, A., and Fornai, F. (2021). The role of cellular prion protein in promoting stemness and differentiation in cancer. Cancers, 13.","DOI":"10.3390\/cancers13020170"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000085064","article-title":"Influence of Different Promoters on the Expression Pattern of Mutated Human \u03b1-Synuclein in Transgenic Mice","volume":"1","author":"Maskri","year":"2004","journal-title":"Neurodegener. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-020-00364-w","article-title":"\u03b1-Synucleinopathy associated c-Abl activation causes p53-dependent autophagy impairment","volume":"15","author":"Karim","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3838","DOI":"10.1021\/acschemneuro.1c00240","article-title":"Accumulation of Prion and Abnormal Prion Protein Induces Hyperphosphorylation of \u03b1-Synuclein in the Brain Tissues from Prion Diseases and in the Cultured Cells","volume":"12","author":"Chen","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_50","first-page":"2779","article-title":"P53 protein expression as prognostic factor in human pancreatic cancer","volume":"17","author":"Sato","year":"1997","journal-title":"Anticancer Res."},{"key":"ref_51","first-page":"279","article-title":"Ki-ras point mutation and p53 expression in human pancreatic cancer: A comparative study among Chinese, Japanese, and Western patients","volume":"9","author":"Dong","year":"2000","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_52","first-page":"1473","article-title":"Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma","volume":"3","author":"Hu","year":"1997","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0002-9440(10)64589-0","article-title":"Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: Comparison with conventional ductal adenocarcinomas","volume":"157","author":"Klimstra","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1097\/00000421-200110000-00016","article-title":"Overexpression of the HER-2\/neu oncogene in pancreatic adenocarcinoma","volume":"24","author":"Safran","year":"2001","journal-title":"Am. J. Clin. Oncol. Cancer Clin. Trials"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/0092-8674(88)90571-5","article-title":"Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes","volume":"53","author":"Almoguera","year":"1988","journal-title":"Cell"},{"key":"ref_56","first-page":"3139","article-title":"Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability","volume":"61","author":"Yamamoto","year":"2001","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41531-021-00273-9","article-title":"Lewy body disease or diseases with Lewy bodies?","volume":"8","author":"Colosimo","year":"2022","journal-title":"NPJ Park. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.parkreldis.2020.11.017","article-title":"Parkinson\u2019s disease and skin","volume":"82","author":"Niemann","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0197-4580(02)00196-3","article-title":"Cell cycle aberrations by \u03b1-synuclein over-expression and cyclin B immunoreactivity in Lewy bodies","volume":"24","author":"Lee","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1093\/hmg\/ddr246","article-title":"Alpha-synuclein functions in the nucleus to protect against hydroxyurea-induced replication stress in yeast","volume":"20","author":"Liu","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bbamem.2011.07.032","article-title":"Biophysics of \u03b1-synuclein membrane interactions","volume":"1818","author":"Pfefferkorn","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.neuropharm.2013.07.035","article-title":"The nuclear accumulation of alpha-synuclein is mediated by importin alpha and promotes neurotoxicity by accelerating the cell cycle","volume":"82","author":"Ma","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jare.2020.01.009","article-title":"Overexpression of alpha-synuclein promotes both cell proliferation and cell toxicity in human SH-SY5Y neuroblastoma cells","volume":"23","author":"Larriva","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Israeli, E., Yakunin, E., Zarbiv, Y., Hacohen-Solovich, A., Kisos, H., Loeb, V., Lichtenstein, M., Ben-Gedalya, T., Sabag, O., and Pikarsky, E. (2011). \u03b1-Synuclein expression selectively affects tumorigenesis in mice modeling Parkinson\u2019s disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019622"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1242\/jcs.122093","article-title":"Role of ser129 phosphorylation of \u03b1-synuclein in melanoma cells","volume":"126","author":"Lee","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.biocel.2015.03.006","article-title":"Alpha-synuclein overexpression negatively regulates insulin receptor substrate 1 by activating mTORC1\/S6K1 signaling","volume":"64","author":"Gao","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Yang, C., Iyaswamy, A., Krishnamoorthi, S., Sreenivasmurthy, S.G., Liu, J., Wang, Z., Tong, B.C.K., Song, J., and Lu, J. (2019). Balancing mTOR signaling and autophagy in the treatment of Parkinson\u2019s disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030728"},{"key":"ref_68","first-page":"413","article-title":"The emerging role of m-TOR up-regulation in brain Astrocytoma","volume":"32","author":"Ryskalin","year":"2017","journal-title":"Histol. Histopathol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Fellner, L., Gabassi, E., Haybaeck, J., and Edenhofer, F. (2021). Autophagy in \u03b1-synucleinopathies\u2014An overstrained system. Cells, 10.","DOI":"10.3390\/cells10113143"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Mavroeidi, P., Arvanitaki, F., Vetsi, M., Becker, S., Vlachakis, D., Jensen, P.H., Stefanis, L., and Xilouri, M. (2022). Autophagy mediates the clearance of oligodendroglial SNCA\/alpha-synuclein and TPPP\/p25A in multiple system atrophy models. Autophagy, 1\u201330.","DOI":"10.1080\/15548627.2021.2016256"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"751568","DOI":"10.3389\/fphar.2021.751568","article-title":"Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma","volume":"12","author":"Raufi","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1097\/PAS.0b013e31824104c5","article-title":"Perineural and intraneural invasion in posttherapy pancreaticoduodenectomy specimens predicts poor prognosis in patients with pancreatic ductal adenocarcinoma","volume":"36","author":"Chatterjee","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_73","first-page":"5","article-title":"Molecular markers associated with perineural invasion in pancreatic ductal adenocarcinoma","volume":"20","author":"Zhang","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1002\/1878-0261.12463","article-title":"Perineural invasion in pancreatic cancer: Proteomic analysis and in vitro modelling","volume":"13","author":"Alrawashdeh","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_75","first-page":"111","article-title":"New insights into perineural invasion of pancreatic cancer: More than pain","volume":"1865","author":"Liang","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11604-006-0115-1","article-title":"Extrapancreatic neural plexus invasion by carcinomas of the pancreatic head region: Evaluation using thinsection helical CT","volume":"25","author":"Tian","year":"2007","journal-title":"Radiat. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:46:05Z","timestamp":1760136365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/7\/3775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,29]]},"references-count":76,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["ijms23073775"],"URL":"https:\/\/doi.org\/10.3390\/ijms23073775","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,29]]}}}