Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein
Abstract Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson’s and Alzheimer’s disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute...
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doaj-7a977155641c4478bcefd6b211a7b1b52021-04-11T11:27:57ZengBMCActa Neuropathologica Communications2051-59602021-04-019111810.1186/s40478-021-01171-0Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion proteinIvan Martinez-Valbuena0Rafael Valenti-Azcarate1Irene Amat-Villegas2Irene Marcilla3Gloria Marti-Andres4Maria-Cristina Caballero5Mario Riverol6María-Teresa Tuñon7Paul E. Fraser8María-Rosario Luquin9Neurosciences Division, Center for Applied Medical Research (CIMA), Universidad de NavarraNeurosciences Division, Center for Applied Medical Research (CIMA), Universidad de NavarraNavarra’s Health Research Institute (IDISNA)Neurosciences Division, Center for Applied Medical Research (CIMA), Universidad de NavarraNavarra’s Health Research Institute (IDISNA)Navarra’s Health Research Institute (IDISNA)Navarra’s Health Research Institute (IDISNA)Pathology Department, Complejo Hospitalario de NavarraTanz Center for Neurodegenerative Diseases, University of TorontoNeurosciences Division, Center for Applied Medical Research (CIMA), Universidad de NavarraAbstract Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson’s and Alzheimer’s disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of α-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and Aβ deposits in the pancreatic tissue of Alzheimer’s disease patients, we studied the immunoreactivity of amylin, tau and α-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic β-cells of these subjects present cooccurrence of misfolded proteins. Furthermore, we also assessed the pancreatic expression of prion protein (PrP) in these subjects and its interaction, both in the pancreas and brain, with α-synuclein, tau, Aβ and amylin. Our study shows, for the first time, that along with amylin, pancreatic α-synuclein, Aβ, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer’s and Parkinson’s disease. Furthermore, we show that the same mixed pathologies that are observed in the brains of patients with neurodegenerative diseases are also present outside the nervous system. Finally, we provide the first histological evidence of an interaction between PrP and Aβ, α-synuclein, amylin or tau in the pancreas and locus coeruleus. These findings will shed more light on the common pathological pathways shared by neurodegenerative diseases and type two diabetes, benefiting the exploration of common therapeutic strategies to prevent or treat these devastating amyloid diseases.https://doi.org/10.1186/s40478-021-01171-0Alpha-synucleinTauPrPType two diabetes mellitusParkinson’s diseaseAlzheimer’s disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ivan Martinez-Valbuena Rafael Valenti-Azcarate Irene Amat-Villegas Irene Marcilla Gloria Marti-Andres Maria-Cristina Caballero Mario Riverol María-Teresa Tuñon Paul E. Fraser María-Rosario Luquin |
spellingShingle |
Ivan Martinez-Valbuena Rafael Valenti-Azcarate Irene Amat-Villegas Irene Marcilla Gloria Marti-Andres Maria-Cristina Caballero Mario Riverol María-Teresa Tuñon Paul E. Fraser María-Rosario Luquin Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein Acta Neuropathologica Communications Alpha-synuclein Tau PrP Type two diabetes mellitus Parkinson’s disease Alzheimer’s disease |
author_facet |
Ivan Martinez-Valbuena Rafael Valenti-Azcarate Irene Amat-Villegas Irene Marcilla Gloria Marti-Andres Maria-Cristina Caballero Mario Riverol María-Teresa Tuñon Paul E. Fraser María-Rosario Luquin |
author_sort |
Ivan Martinez-Valbuena |
title |
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
title_short |
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
title_full |
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
title_fullStr |
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
title_full_unstemmed |
Mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
title_sort |
mixed pathologies in pancreatic β cells from subjects with neurodegenerative diseases and their interaction with prion protein |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2021-04-01 |
description |
Abstract Protein misfolding diseases refer to a variety of disorders that develop as a consequence of the misfolding of proteins in various organs. The etiologies of Parkinson’s and Alzheimer’s disease remain unclear, but it seems that type two diabetes and other prediabetic states could contribute to the appearance of the sporadic forms of these diseases. In addition to amylin deposition, other amyloidogenic proteins implicated in the pathophysiology of neurodegenerative diseases could have important roles in the pathogenesis of this disease. As we have previously demonstrated the presence of α-synuclein deposits in the pancreas of patients with synucleinopathies, as well as tau and Aβ deposits in the pancreatic tissue of Alzheimer’s disease patients, we studied the immunoreactivity of amylin, tau and α-synuclein in the pancreas of 138 subjects with neurodegenerative diseases or type two diabetes and assessed whether the pancreatic β-cells of these subjects present cooccurrence of misfolded proteins. Furthermore, we also assessed the pancreatic expression of prion protein (PrP) in these subjects and its interaction, both in the pancreas and brain, with α-synuclein, tau, Aβ and amylin. Our study shows, for the first time, that along with amylin, pancreatic α-synuclein, Aβ, PrP and tau may contribute together to the complex pathophysiology of type two diabetes and in the appearance of insulin resistance in Alzheimer’s and Parkinson’s disease. Furthermore, we show that the same mixed pathologies that are observed in the brains of patients with neurodegenerative diseases are also present outside the nervous system. Finally, we provide the first histological evidence of an interaction between PrP and Aβ, α-synuclein, amylin or tau in the pancreas and locus coeruleus. These findings will shed more light on the common pathological pathways shared by neurodegenerative diseases and type two diabetes, benefiting the exploration of common therapeutic strategies to prevent or treat these devastating amyloid diseases. |
topic |
Alpha-synuclein Tau PrP Type two diabetes mellitus Parkinson’s disease Alzheimer’s disease |
url |
https://doi.org/10.1186/s40478-021-01171-0 |
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