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dc.contributor.authorMoreno-Gonzalez I., Edwards G., III, Shahnawaz M., Diaz-Espinoza R., Soto C.es_CL
dc.contributor.authorSalvadores, N. [Centro de Biología Integrativa, Facultad de Ciencias, Universidad Mayor, Chile]es_CL
dc.date.accessioned2020-08-12T14:11:55Z
dc.date.accessioned2020-08-12T18:13:28Z
dc.date.available2020-08-12T14:11:55Z
dc.date.available2020-08-12T18:13:28Z
dc.date.issued2017es_CL
dc.identifier.citationMoreno-Gonzalez, I., Edwards III, G., Salvadores, N., Shahnawaz, M., Diaz-Espinoza, R., & Soto, C. (2017). Molecular interaction between type 2 diabetes and Alzheimer’s disease through cross-seeding of protein misfolding. Molecular psychiatry, 22(9), 1327-1334.es_CL
dc.identifier.issn1359-4184es_CL
dc.identifier.issn1476-5578es_CL
dc.identifier.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495631/pdf/nihms823458.pdfes_CL
dc.identifier.urihttps://dx.doi.org/10.1038%2Fmp.2016.230es_CL
dc.identifier.urihttp://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5495631&blobtype=pdfes_CL
dc.identifier.urihttp://repositorio.umayor.cl/xmlui/handle/sibum/6930
dc.description.abstractNumerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (A beta) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein. Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-seeding A beta, providing a molecular explanation for the link between these diseases. Here, we examined how misfolded IAPP affects A beta aggregation and AD pathology in vitro and in vivo. We observed that addition of IAPP seeds accelerates A beta aggregation in vitro in a seeding-like manner and the resulting fibrils are composed of both peptides. Transgenic animals expressing both human proteins exhibited exacerbated AD-like pathology compared with AD transgenic mice or AD transgenic animals with type 1 diabetes (T1D). Remarkably, IAPP colocalized with amyloid plaques in brain parenchymal deposits, suggesting that these peptides may directly interact and aggravate the disease. Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice resulted in more severe AD pathology and significantly greater memory impairments than untreated animals. These data provide a proof-of-concept for a new disease mechanism involving the interaction of misfolded proteins through cross-seeding events which may contribute to accelerate or exacerbate disease pathogenesis. Our findings could shed light on understanding the linkage between T2D and AD, two of the most prevalent protein misfolding disorders.es_CL
dc.description.sponsorshipWe thank Dr Peter C Butler (University of California at Los Angeles) for the donation of the IAPP diabetic colony and Dr Charles Mays (University of Texas Medical School at Houston) for extensive editing of the manuscript. This work was partially funded by NIH grant R01GM100453 to CS.es_CL
dc.format.extentArtículo original
dc.language.isoenes_CL
dc.publisherNature Publishing Groupes_CL
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceMolecular Psychiatry, 2017. 22(9): p: 1327-1334
dc.titleMolecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfoldinges_CL
dc.typeArtículo o paperes_CL
umayor.facultadFacultad de Ciencias
umayor.indizadorCOT
umayor.politicas.sherpa/romeoEsta revista tiene licencia Creative Commons BYes_CL
umayor.indexadoWOSes_CL
umayor.indexadoSCOPUSes_CL
dc.identifier.doiDOI: 10.1038/mp.2016.230es_CL]
umayor.indicadores.wos-(cuartil)Q1es_CL
umayor.indicadores.scopus-(scimago-sjr)6,29es_CL
umayor.indicadores.scopus-(scimago-sjr)ÍNDICE H: 432es_CL


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