{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:03:28Z","timestamp":1788498208603,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T00:00:00Z","timestamp":1643760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1DK091845"],"award-info":[{"award-number":["RO1DK091845"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Amyloidosis is a common pathological event in which proteins self-assemble into misfolded soluble and insoluble molecular forms, oligomers and fibrils that are often toxic to cells. Notably, aggregation-prone human islet amyloid polypeptide (hIAPP), or amylin, is a pancreatic hormone linked to islet \u03b2-cells demise in diabetics. The unifying mechanism by which amyloid proteins, including hIAPP, aggregate and kill cells is still matter of debate. The pathology of type-2 diabetes mellitus (T2DM) is characterized by extracellular and intracellular accumulation of toxic hIAPP species, soluble oligomers and insoluble fibrils in pancreatic human islets, eventually leading to loss of \u03b2-cell mass. This review focuses on molecular, biochemical and cell-biology studies exploring molecular mechanisms of hIAPP synthesis, trafficking and degradation in the pancreas. In addition to hIAPP turnover, the dynamics and the mechanisms of IAPP\u2013membrane interactions; hIAPP aggregation and toxicity in vitro and in situ; and the regulatory role of diabetic factors, such as lipids and cholesterol, in these processes are also discussed.<\/jats:p>","DOI":"10.3390\/molecules27031021","type":"journal-article","created":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T05:42:33Z","timestamp":1643866953000},"page":"1021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas"],"prefix":"10.3390","volume":"27","author":[{"given":"Diti Chatterjee","family":"Bhowmick","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Endocrinology, Diabetes and Metabolism Research Institute, City of Hope\u2019s Beckman Research Institute, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanar","family":"Kudaibergenova","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar M.","family":"Jeremic","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","first-page":"101","article-title":"Amyloid fibril protein nomenclature: 2010 recommendations from the nomenclature committee of the International Society of Amyloidosis","volume":"17","author":"Sipe","year":"2010","journal-title":"Amyloid Int. J. Exp. Clin. Investig. Off. J. Int. Soc. Amyloidosis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.jinorgbio.2011.05.013","article-title":"Physiological cholesterol concentration is a neuroprotective factor against beta-amyloid and beta-amyloid-metal complexes toxicity","volume":"105","author":"Granzotto","year":"2011","journal-title":"J. Inorg. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1016\/j.bbamem.2007.05.004","article-title":"Membrane interactions and the effect of metal ions of the amyloidogenic fragment Abeta(25-35) in comparison to Abeta(1-42)","volume":"1768","author":"Lau","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1046\/j.1471-4159.2000.0752536.x","article-title":"The role of prion peptide structure and aggregation in toxicity and membrane binding","volume":"75","author":"Rymer","year":"2000","journal-title":"J. Neurochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1152\/physrev.00042.2009","article-title":"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus","volume":"91","author":"Westermark","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1021\/acs.chemrev.0c00981","article-title":"Proteostasis of islet amyloid polypeptide: A molecular perspective of risk factors and protective strategies for type II diabetes","volume":"121","author":"Milardi","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15019","DOI":"10.1038\/nrdp.2015.19","article-title":"Type 2 diabetes mellitus","volume":"1","author":"DeFronzo","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","first-page":"4047","article-title":"Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes","volume":"86","author":"Kahn","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s00125-003-1304-4","article-title":"Islet amyloid: A complication of islet dysfunction or an aetiological factor in Type 2 diabetes?","volume":"47","author":"Clark","year":"2004","journal-title":"Diabetologia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"304","DOI":"10.2337\/db06-0430","article-title":"Identification of the amyloid-degrading enzyme neprilysin in mouse islets and potential role in islet amyloidogenesis","volume":"56","author":"Zraika","year":"2007","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52810","DOI":"10.1074\/jbc.M308244200","article-title":"Fibrillogenic amylin evokes islet beta-cell apoptosis through linked activation of a caspase cascade and JNK1","volume":"278","author":"Zhang","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2337\/db06-0734","article-title":"Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets","volume":"56","author":"Ritzel","year":"2007","journal-title":"Diabetes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.bbagen.2009.02.013","article-title":"Amyloid inhibitors enhance survival of cultured human islets","volume":"1790","author":"Potter","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7283","DOI":"10.1073\/pnas.93.14.7283","article-title":"Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide","volume":"93","author":"Janson","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0022-2836(02)01044-6","article-title":"Increased expression and activation of c-Jun contributes to human amylin-induced apoptosis in pancreatic islet beta-cells","volume":"324","author":"Zhang","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.2337\/db07-0197","article-title":"High expression rates of human islet amyloid polypeptide induce endoplasmic reticulum stress mediated beta-cell apoptosis, a characteristic of humans with type 2 but not type 1 diabetes","volume":"56","author":"Huang","year":"2007","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1007\/s00125-008-1111-z","article-title":"Calcium elevation in mouse pancreatic beta cells evoked by extracellular human islet amyloid polypeptide involves activation of the mechanosensitive ion channel TRPV4","volume":"51","author":"Casas","year":"2008","journal-title":"Diabetologia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12680","DOI":"10.1021\/bi801427c","article-title":"A single mutation in the nonamyloidogenic region of islet amyloid polypeptide greatly reduces toxicity","volume":"47","author":"Brender","year":"2008","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1354\/vp.45-1-67","article-title":"Transthyretin amyloidosis and two other aging-related amyloidoses in an aged vervet monkey","volume":"45","author":"Nakamura","year":"2008","journal-title":"Vet. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"13992","DOI":"10.1073\/pnas.0906471106","article-title":"Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons","volume":"106","author":"Davalli","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"151","article-title":"Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: Quantitative changes in the pancreas in type 2 diabetes","volume":"9","author":"Clark","year":"1988","journal-title":"Diabetes Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/BF01660981","article-title":"Immunohistology of islet amyloid polypeptide in diabetes mellitus: Semi-quantitative studies in a post-mortem series","volume":"421","author":"Rocken","year":"1992","journal-title":"Virchows Arch. A Pathol. Anat. Histopathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","article-title":"Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes","volume":"52","author":"Butler","year":"2003","journal-title":"Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.molmed.2015.04.005","article-title":"Type 2 diabetes as a protein misfolding disease","volume":"21","author":"Mukherjee","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1615\/CritRevNeurobiol.v11.i2-3.40","article-title":"Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: A peptide superfamily","volume":"11","author":"Wimalawansa","year":"1997","journal-title":"Crit. Rev. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/0014-5793(90)80314-9","article-title":"The human islet amyloid polypeptide (IAPP) gene. Organization, chromosomal localization and functional identification of a promoter region","volume":"267","author":"Christmanson","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/0014-5793(89)81260-8","article-title":"The complete islet amyloid polypeptide precursor is encoded by two exons","volume":"247","author":"Mosselman","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/286082a0","article-title":"The insulin gene is located on chromosome 11 in humans","volume":"286","author":"Owerbach","year":"1980","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.mam.2015.01.001","article-title":"Proinsulin misfolding and endoplasmic reticulum stress during the development and progression of diabetes","volume":"42","author":"Sun","year":"2015","journal-title":"Mol. Asp. Med."},{"key":"ref_31","unstructured":"Feingold, K.R., Anawalt, B., Boyce, A., Chrousos, G., Dungan, K., Grossman, A., Hershman, J.M., Kaltsas, G., Koch, C., and Kopp, P. (2000). Insulin biosynthesis, secretion, structure, and structure-activity relationships. Endotext, MDText.com, Inc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1042\/BCJ20200984","article-title":"FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic beta-cells","volume":"478","author":"Burnett","year":"2021","journal-title":"Biochem. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1016\/j.bbamem.2018.03.024","article-title":"Apoptosis signal regulating kinase-1 and NADPH oxidase mediate human amylin evoked redox stress and apoptosis in pancreatic beta-cells","volume":"1860","author":"Singh","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_34","first-page":"E1008","article-title":"Islet amyloid polypeptide and insulin gene expression are regulated in parallel by glucose in vivo in rats","volume":"271","author":"Mulder","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1210\/en.2002-220564","article-title":"Oligonucleotide microarray analysis of intact human pancreatic islets: Identification of glucose-responsive genes and a highly regulated TGFbeta signaling pathway","volume":"143","author":"Shalev","year":"2002","journal-title":"Endocrinology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0167-0115(96)02109-X","article-title":"Signals related to glucose metabolism regulate islet amyloid polypeptide (IAPP) gene expression in human pancreatic islets","volume":"68","author":"Gasa","year":"1997","journal-title":"Regul. Pept."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11807","DOI":"10.1074\/jbc.M113.525022","article-title":"Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2","volume":"289","author":"Jing","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.bbaexp.2004.09.009","article-title":"Transcriptional regulation of the IAPP gene in pancreatic beta-cells","volume":"1681","author":"Shepherd","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15330","DOI":"10.1074\/jbc.M908045199","article-title":"Glucose regulates islet amyloid polypeptide gene transcription in a PDX1- and calcium-dependent manner","volume":"275","author":"Macfarlane","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1006\/bbrc.1996.1875","article-title":"Involvement of the homeodomain-containing transcription factor PDX-1 in islet amyloid polypeptide gene transcription","volume":"229","author":"Watada","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.2337\/db06-0788","article-title":"Comparative analysis of insulin gene promoters: Implications for diabetes research","volume":"55","author":"Hay","year":"2006","journal-title":"Diabetes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"22228","DOI":"10.1074\/jbc.M312673200","article-title":"Identification of a novel PDX-1 binding site in the human insulin gene enhancer","volume":"279","author":"Matsuoka","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"243","article-title":"Activation of amylin gene transcription by LIM domain homeobox gene isl-1","volume":"10","author":"Wang","year":"1996","journal-title":"Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1007\/s00018-006-6095-6","article-title":"The Foxa family of transcription factors in development and metabolism","volume":"63","author":"Friedman","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3389\/fnins.2015.00216","article-title":"Amylin at the interface between metabolic and neurodegenerative disorders","volume":"9","author":"Lutz","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0091-679X(08)00813-3","article-title":"Nano-scale imaging and dynamics of amylin-membrane interactions and its implication in type II diabetes mellitus","volume":"90","author":"Cho","year":"2008","journal-title":"Methods Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/nm.3287","article-title":"Thioredoxin-interacting protein regulates insulin transcription through microRNA-204","volume":"19","author":"Xu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"732","DOI":"10.15252\/emmm.201302561","article-title":"Thioredoxin-interacting protein regulates protein disulfide isomerases and endoplasmic reticulum stress","volume":"6","author":"Lee","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cmet.2012.07.005","article-title":"Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome","volume":"16","author":"Oslowski","year":"2012","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14210","DOI":"10.1074\/jbc.RA118.002414","article-title":"Functional proteasome complex is required for turnover of islet amyloid polypeptide in pancreatic beta-cells","volume":"293","author":"Jeremic","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.cell.2007.04.040","article-title":"A mammalian microRNA expression atlas based on small RNA library sequencing","volume":"129","author":"Landgraf","year":"2007","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e188","DOI":"10.1093\/nar\/gnh186","article-title":"Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs","volume":"32","author":"Sun","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/ncb0309-228","article-title":"Many roads to maturity: microRNA biogenesis pathways and their regulation","volume":"11","author":"Winter","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.cmet.2013.11.016","article-title":"Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets","volume":"19","author":"Kameswaran","year":"2014","journal-title":"Cell Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1073\/pnas.84.11.3881","article-title":"Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells","volume":"84","author":"Westermark","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00125-014-3257-1","article-title":"Impaired proteostasis: Role in the pathogenesis of diabetes mellitus","volume":"57","author":"Jaisson","year":"2014","journal-title":"Diabetologia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.bpj.2013.07.029","article-title":"Effect of proline mutations on the monomer conformations of amylin","volume":"105","author":"Chiu","year":"2013","journal-title":"Biophys. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1021\/bi981658g","article-title":"Effects of sequential proline substitutions on amyloid formation by human amylin20-29","volume":"38","author":"Moriarty","year":"1999","journal-title":"Biochemistry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1073\/pnas.87.13.5036","article-title":"Islet amyloid polypeptide: Pinpointing amino acid residues linked to amyloid fibril formation","volume":"87","author":"Westermark","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"16284","DOI":"10.1021\/bi051432v","article-title":"The role of His-18 in amyloid formation by human islet amyloid polypeptide","volume":"44","author":"Abedini","year":"2005","journal-title":"Biochemistry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1021\/bi3014278","article-title":"Role of aromatic interactions in amyloid formation by islet amyloid polypeptide","volume":"52","author":"Tu","year":"2013","journal-title":"Biochemistry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jmb.2011.12.032","article-title":"Sensitivity of amyloid formation by human islet amyloid polypeptide to mutations at residue 20","volume":"421","author":"Cao","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19279","DOI":"10.1073\/pnas.1305517110","article-title":"Islet amyloid polypeptide toxicity and membrane interactions","volume":"110","author":"Cao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2337\/diabetes.48.3.491","article-title":"The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles","volume":"48","author":"Janson","year":"1999","journal-title":"Diabetes"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1111\/j.1742-4658.2006.05367.x","article-title":"The aggregation potential of human amylin determines its cytotoxicity towards islet beta-cells","volume":"273","author":"Konarkowska","year":"2006","journal-title":"FEBS J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"36086","DOI":"10.1074\/jbc.M111.240762","article-title":"Clustering and internalization of toxic amylin oligomers in pancreatic cells require plasma membrane cholesterol","volume":"286","author":"Trikha","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5083","DOI":"10.1096\/fj.14-251744","article-title":"The pathogenic mechanism of diabetes varies with the degree of overexpression and oligomerization of human amylin in the pancreatic islet beta cells","volume":"28","author":"Zhang","year":"2014","journal-title":"FASEB J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2337\/db10-0522","article-title":"beta-cell dysfunctional ERAD\/ubiquitin\/proteasome system in type 2 diabetes mediated by islet amyloid polypeptide-induced UCH-L1 deficiency","volume":"60","author":"Costes","year":"2011","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1080\/10409230802605914","article-title":"Diverse regulatory mechanisms of eukaryotic transcriptional activation by the proteasome complex","volume":"43","author":"Bhaumik","year":"2008","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bbagrm.2010.08.001","article-title":"The proteasome and its regulatory roles in gene expression","volume":"1809","author":"Kwak","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1042\/BCJ20160026","article-title":"Proteasome regulates turnover of toxic human amylin in pancreatic cells","volume":"473","author":"Singh","year":"2016","journal-title":"Biochem. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.2337\/db07-0178","article-title":"Impairment of the ubiquitin-proteasome pathway is a downstream endoplasmic reticulum stress response induced by extracellular human islet amyloid polypeptide and contributes to pancreatic beta-cell apoptosis","volume":"56","author":"Casas","year":"2007","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.4161\/auto.28478","article-title":"UCHL1 deficiency exacerbates human islet amyloid polypeptide toxicity in beta-cells: Evidence of interplay between the ubiquitin\/proteasome system and autophagy","volume":"10","author":"Costes","year":"2014","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1172\/JCI69625","article-title":"Amyloidogenic peptide oligomer accumulation in autophagy-deficient beta cells induces diabetes","volume":"124","author":"Kim","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1172\/JCI71981","article-title":"Autophagy defends pancreatic beta cells from human islet amyloid polypeptide-induced toxicity","volume":"124","author":"Rivera","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/cdd.2010.111","article-title":"Human-IAPP disrupts the autophagy\/lysosomal pathway in pancreatic beta-cells: Protective role of p62-positive cytoplasmic inclusions","volume":"18","author":"Rivera","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mad.2018.03.010","article-title":"Protein aggregates and proteostasis in aging: Amylin and beta-cell function","volume":"177","author":"Press","year":"2019","journal-title":"Mech. Ageing Dev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"36621","DOI":"10.1074\/jbc.M006170200","article-title":"Degradation of amylin by insulin-degrading enzyme","volume":"275","author":"Bennett","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.2337\/diabetes.52.9.2315","article-title":"An insulin-degrading enzyme inhibitor decreases amylin degradation, increases amylin-induced cytotoxicity, and increases amyloid formation in insulinoma cell cultures","volume":"52","author":"Bennett","year":"2003","journal-title":"Diabetes"},{"key":"ref_80","first-page":"608","article-title":"Insulin degradation: Progress and potential","volume":"19","author":"Duckworth","year":"1998","journal-title":"Endocr. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3462","DOI":"10.1210\/en.2016-1410","article-title":"Inhibition of insulin-degrading enzyme does not increase islet amyloid deposition in vitro","volume":"157","author":"Hogan","year":"2016","journal-title":"Endocrinology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3553","DOI":"10.1074\/jbc.M112.438457","article-title":"Matrix metalloproteinase-9 reduces islet amyloid formation by degrading islet amyloid polypeptide","volume":"288","author":"Zraika","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"18177","DOI":"10.1074\/jbc.M109.082032","article-title":"Neprilysin impedes islet amyloid formation by inhibition of fibril formation rather than peptide degradation","volume":"285","author":"Zraika","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.jmb.2009.08.055","article-title":"Cholesterol regulates assembly of human islet amyloid polypeptide on model membranes","volume":"393","author":"Cho","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.jmb.2004.06.086","article-title":"Phospholipid catalysis of diabetic amyloid assembly","volume":"341","author":"Knight","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s001250051295","article-title":"Amyloid fibril formation is progressive and correlates with beta-cell secretion in transgenic mouse isolated islets","volume":"42","author":"MacArthur","year":"1999","journal-title":"Diabetologia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1021\/ja710484d","article-title":"Amyloid fiber formation and membrane disruption are separate processes localized in two distinct regions of IAPP, the type-2-diabetes-related peptide","volume":"130","author":"Brender","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"421287","DOI":"10.1155\/2008\/421287","article-title":"Recent insights in islet amyloid polypeptide-induced membrane disruption and its role in beta-cell death in type 2 diabetes mellitus","volume":"2008","author":"Khemtemourian","year":"2008","journal-title":"Exp. Diabetes Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"12113","DOI":"10.1021\/bi050840w","article-title":"Lipid membranes modulate the structure of islet amyloid polypeptide","volume":"44","author":"Jayasinghe","year":"2005","journal-title":"Biochemistry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.bbamem.2007.01.022","article-title":"Membrane interaction of islet amyloid polypeptide","volume":"1768","author":"Jayasinghe","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9496","DOI":"10.1021\/bi060579z","article-title":"Conserved and cooperative assembly of membrane-bound alpha-helical states of islet amyloid polypeptide","volume":"45","author":"Knight","year":"2006","journal-title":"Biochemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1021\/bi0160462","article-title":"Islet amyloid: Phase partitioning and secondary nucleation are central to the mechanism of fibrillogenesis","volume":"41","author":"Padrick","year":"2002","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Almeida, Z.L., and Brito, R.M.M. (2020). Structure and aggregation mechanisms in amyloids. Molecules, 25.","DOI":"10.3390\/molecules25051195"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10427","DOI":"10.1073\/pnas.0502066102","article-title":"Amyloid ion channels: A common structural link for protein-misfolding disease","volume":"102","author":"Quist","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1210\/er.2007-0037","article-title":"Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis","volume":"29","author":"Haataja","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1074\/jbc.271.4.1988","article-title":"Pore formation by the cytotoxic islet amyloid peptide amylin","volume":"271","author":"Mirzabekov","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2368","DOI":"10.1039\/C3CP53345J","article-title":"Non-selective ion channel activity of polymorphic human islet amyloid polypeptide (amylin) double channels","volume":"16","author":"Zhao","year":"2014","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bpj.2016.05.050","article-title":"The role of cholesterol in driving IAPP-membrane interactions","volume":"111","author":"Sciacca","year":"2016","journal-title":"Biophys. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0925-4439(01)00078-3","article-title":"Islet amyloid and type 2 diabetes: From molecular misfolding to islet pathophysiology","volume":"1537","author":"Jaikaran","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/35036052","article-title":"Lipid rafts and signal transduction","volume":"1","author":"Simons","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0006-3495(97)78067-6","article-title":"The influence of cholesterol on phospholipid membrane curvature and bending elasticity","volume":"73","author":"Chen","year":"1997","journal-title":"Biophys. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1021\/ja809002a","article-title":"Induction of negative curvature as a mechanism of cell toxicity by amyloidogenic peptides: The case of islet amyloid polypeptide","volume":"131","author":"Smith","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"657946","DOI":"10.3389\/fmolb.2021.657946","article-title":"The effect of cholesterol on membrane-bound islet amyloid polypeptide","volume":"8","author":"Christensen","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1021\/acs.biochem.6b01016","article-title":"Islet amyloid polypeptide membrane interactions: Effects of membrane composition","volume":"56","author":"Zhang","year":"2017","journal-title":"Biochemistry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jmb.2005.12.020","article-title":"Islet amyloid polypeptide inserts into phospholipid monolayers as monomer","volume":"356","author":"Engel","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"96837","DOI":"10.1039\/C6RA19714K","article-title":"Interactions of the N-terminal domain of human islet amyloid polypeptide with lipid membranes: The effect of cholesterol","volume":"6","author":"Li","year":"2016","journal-title":"RSC Adv."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1021\/acs.biochem.7b01190","article-title":"Sterol structure strongly modulates membrane-islet amyloid polypeptide interactions","volume":"57","author":"Zhang","year":"2018","journal-title":"Biochemistry"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Trikha, S., and Jeremic, A.M. (2013). Distinct internalization pathways of human amylin monomers and its cytotoxic oligomers in pancreatic cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073080"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1007\/s00125-016-3907-6","article-title":"ABCA1 deficiency and cellular cholesterol accumulation increases islet amyloidogenesis in mice","volume":"59","author":"Wijesekara","year":"2016","journal-title":"Diabetologia"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"4336","DOI":"10.1021\/acschemneuro.0c00588","article-title":"Lipid-chaperone hypothesis: A common molecular mechanism of membrane disruption by intrinsically disordered proteins","volume":"11","author":"Sciacca","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"184901","DOI":"10.1063\/1.4948323","article-title":"Lipid-assisted protein transport: A diffusion-reaction model supported by kinetic experiments and molecular dynamics simulations","volume":"144","author":"Scalisi","year":"2016","journal-title":"J. Chem. Phys."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5125","DOI":"10.1021\/acs.jpclett.8b02241","article-title":"Phospholipids critical micellar concentrations trigger different mechanisms of intrinsically disordered proteins interaction with model membranes","volume":"9","author":"Scollo","year":"2018","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12933-018-0672-5","article-title":"Relationship between polyunsaturated fatty acid composition in serum phospholipids, systemic low-grade inflammation, and glycemic control in patients with type 2 diabetes and atherosclerotic cardiovascular disease","volume":"17","author":"Poreba","year":"2018","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jmb.2003.10.045","article-title":"The mechanism of insulin action on islet amyloid polypeptide fiber formation","volume":"335","author":"Larson","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8973","DOI":"10.1021\/ja1007867","article-title":"Role of zinc in human islet amyloid polypeptide aggregation","volume":"132","author":"Brender","year":"2010","journal-title":"J. Am. Chem. Soc."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"9394","DOI":"10.1039\/C7CC04291D","article-title":"Zinc-coordination and C-peptide complexation: A potential mechanism for the endogenous inhibition of IAPP aggregation","volume":"53","author":"Ge","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.bbapap.2018.11.006","article-title":"Zinc boosts EGCG\u2019s hIAPP amyloid inhibition both in solution and membrane","volume":"1867","author":"Lee","year":"2019","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"8240","DOI":"10.1038\/srep08240","article-title":"Inhibition of IAPP aggregation by insulin depends on the insulin oligomeric state regulated by zinc ion concentration","volume":"5","author":"Ding","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"105083","DOI":"10.1016\/j.chemphyslip.2021.105083","article-title":"Investigation of the effects of two major secretory granules components, insulin and zinc, on human-IAPP amyloid aggregation and membrane damage","volume":"237","author":"Khemtemourian","year":"2021","journal-title":"Chem. Phys. Lipids"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"12558","DOI":"10.1039\/c3cp44542a","article-title":"Copper(II)-human amylin complex protects pancreatic cells from amylin toxicity","volume":"15","author":"Lee","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"9829","DOI":"10.1021\/acs.analchem.5b02217","article-title":"Rapid assessment of human amylin aggregation and its inhibition by copper(II) ions by laser ablation electrospray ionization mass spectrometry with ion mobility separation","volume":"87","author":"Li","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1039\/C4MT00021H","article-title":"Inhibition of human amylin fibril formation by insulin-mimetic vanadium complexes","volume":"6","author":"He","year":"2014","journal-title":"Metallomics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jinorgbio.2018.11.004","article-title":"Interaction of amylin species with transition metals and membranes","volume":"191","author":"Alghrably","year":"2019","journal-title":"J. Inorg. Biochem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2046327","DOI":"10.1155\/2016\/2046327","article-title":"Inhibition of IAPP aggregation and toxicity by natural products and derivatives","volume":"2016","author":"Pithadia","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s41598-017-18807-8","article-title":"Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice","volume":"8","author":"Franko","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"33076","DOI":"10.1038\/srep33076","article-title":"Conformational ensemble of hIAPP dimer: Insight into the molecular mechanism by which a green tea extract inhibits hIAPP aggregation","volume":"6","author":"Mo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/cphc.201700057","article-title":"Inhibitory mechanism of epigallocatechin gallate on fibrillation and aggregation of amidated human islet amyloid polypeptide","volume":"18","author":"Xu","year":"2017","journal-title":"ChemPhysChem"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.ejmech.2015.01.047","article-title":"Resveratrol interferes with the aggregation of membrane-bound human-IAPP: A molecular dynamics study","volume":"92","author":"Lolicato","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/j.bbamem.2018.03.012","article-title":"A blend of two resveratrol derivatives abolishes hIAPP amyloid growth and membrane damage","volume":"1860","author":"Sciacca","year":"2018","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.1039\/C5FO00500K","article-title":"Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress","volume":"6","author":"Yu","year":"2015","journal-title":"Food Funct."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-12679-1_1","article-title":"Neuroanatomy and pathology of sporadic Alzheimer\u2019s disease","volume":"215","author":"Braak","year":"2015","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S1474-4422(09)70238-8","article-title":"Neuropathological assessment of Parkinson\u2019s disease: Refining the diagnostic criteria","volume":"8","author":"Dickson","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.bbadis.2014.05.003","article-title":"The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: Implications for Alzheimer\u2019s disease","volume":"1842","author":"Placido","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988","article-title":"Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal","volume":"8","author":"Maroteaux","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1006\/jmbi.2001.4538","article-title":"Conformational properties of alpha-synuclein in its free and lipid-associated states","volume":"307","author":"Eliezer","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0896-6273(95)90302-X","article-title":"The precursor protein of non-A beta component of Alzheimer\u2019s disease amyloid is a presynaptic protein of the central nervous system","volume":"14","author":"Iwai","year":"1995","journal-title":"Neuron"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Wang, Y., and Westermark, G.T. (2021). The amyloid forming peptides islet amyloid polypeptide and amyloid beta interact at the molecular level. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011153"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s10495-011-0656-3","article-title":"beta-Amyloid protein (Abeta) and human amylin regulation of apoptotic genes occurs through the amylin receptor","volume":"17","author":"Jhamandas","year":"2012","journal-title":"Apoptosis"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1326-9-30","article-title":"Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin","volume":"9","author":"Srodulski","year":"2014","journal-title":"Mol. Neurodegener."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Rosas, P.C., Nagaraja, G.M., Kaur, P., Panossian, A., Wickman, G., Garcia, L.R., Al-Khamis, F.A., and Asea, A.A. (2016). Hsp72 (HSPA1A) prevents human islet amyloid polypeptide aggregation and toxicity: A new approach for type 2 diabetes treatment. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149409"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Schultz, S.W., Nilsson, K.P., and Westermark, G.T. (2011). Drosophila melanogaster as a model system for studies of islet amyloid polypeptide aggregation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020221"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.neulet.2019.04.016","article-title":"An inducible model of human amylin overexpression reveals diverse transcriptional changes","volume":"704","author":"Aldras","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/ana.23956","article-title":"Amylin deposition in the brain: A second amyloid in Alzheimer disease?","volume":"74","author":"Jackson","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Lu, L., Fu, D.L., Li, H.Q., Liu, A.J., Li, J.H., and Zheng, G.Q. (2014). Diabetes and risk of Parkinson\u2019s disease: An updated meta-analysis of case-control studies. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0085781"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s40478-021-01171-0","article-title":"Mixed pathologies in pancreatic beta cells from subjects with neurodegenerative diseases and their interaction with prion protein","volume":"9","author":"Marcilla","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.2337\/diabetes.51.4.1256","article-title":"Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study","volume":"51","author":"Peila","year":"2002","journal-title":"Diabetes"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.parkreldis.2021.06.002","article-title":"Prediabetes, type 2 diabetes mellitus and risk of Parkinson\u2019s disease: A population-based cohort study","volume":"89","author":"Diaz","year":"2021","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fnagi.2013.00038","article-title":"Lessons from two prevalent amyloidosis\u2014What amylin and Abeta have in common","volume":"5","author":"Gotz","year":"2013","journal-title":"Front. Aging Neurosci."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"12473","DOI":"10.1073\/pnas.1610371113","article-title":"Cross-talk between amyloidogenic proteins in type-2 diabetes and Parkinson\u2019s disease","volume":"113","author":"Horvath","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"20438","DOI":"10.1038\/s41598-020-77409-z","article-title":"alpha-Synuclein promotes IAPP fibril formation in vitro and beta-cell amyloid formation in vivo in mice","volume":"10","author":"Mucibabic","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/s41586-018-0104-4","article-title":"Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies","volume":"557","author":"Peng","year":"2018","journal-title":"Nature"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00401-021-02316-0","article-title":"Multiple system atrophy-associated oligodendroglial protein p25alpha stimulates formation of novel alpha-synuclein strain with enhanced neurodegenerative potential","volume":"142","author":"Ferreira","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","article-title":"Idiopathic Parkinson\u2019s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen","volume":"110","author":"Braak","year":"2003","journal-title":"J. Neural Transm."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/brain\/awab061","article-title":"Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats","volume":"144","author":"Ferreira","year":"2021","journal-title":"Brain"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40478-021-01131-8","article-title":"Trans-synaptic spreading of alpha-synuclein pathology through sensory afferents leads to sensory nerve degeneration and neuropathic pain","volume":"9","author":"Ferreira","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1084\/jem.20161134","article-title":"Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism","volume":"214","author":"Mukherjee","year":"2017","journal-title":"J. Exp. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/3\/1021\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:13:08Z","timestamp":1760134388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/3\/1021"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,2]]},"references-count":156,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["molecules27031021"],"URL":"https:\/\/doi.org\/10.3390\/molecules27031021","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,2]]}}}