Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease
Diabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It cont...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2020.00035/full |
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| author | Ana F. Raimundo Ana F. Raimundo Ana F. Raimundo Sofia Ferreira Sofia Ferreira Ivo C. Martins Regina Menezes Regina Menezes Regina Menezes |
| author_facet | Ana F. Raimundo Ana F. Raimundo Ana F. Raimundo Sofia Ferreira Sofia Ferreira Ivo C. Martins Regina Menezes Regina Menezes Regina Menezes |
| author_sort | Ana F. Raimundo |
| collection | DOAJ |
| description | Diabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It contributes to the maintenance of glucose physiological levels namely by inhibiting insulin and glucagon secretion as well as controlling adiposity and satiation. IAPP is a highly amyloidogenic polypeptide forming intracellular aggregates and amyloid structures that are associated with β-cell death. Data also suggest the relevance of unprocessed IAPP forms as seeding for amyloid buildup. Besides the known consequences of hyperamylinemia in the pancreas, evidence has also pointed out that IAPP has a pathological role in cognitive function. More specifically, IAPP was shown to impair the blood–brain barrier; it was also seen to interact and co-deposit with amyloid beta peptide (Aß), and possibly with Tau, within the brain of Alzheimer's disease (AD) patients, thereby contributing to diabetes-associated dementia. In fact, it has been suggested that AD results from a metabolic dysfunction in the brain, leading to its proposed designation as type 3 diabetes. Here, we have first provided a brief perspective on the IAPP amyloidogenic process and its role in diabetes and AD. We have then discussed the potential interventions for modulating IAPP proteotoxicity that can be explored for therapeutics. Finally, we have proposed the concept of a “diabetes brain phenotype” hypothesis in AD, which may help design future IAPP-centered drug developmentstrategies against AD. |
| first_indexed | 2024-04-12T00:11:32Z |
| format | Article |
| id | doaj.art-86adeed75b2449c8acf634640b989419 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-12T00:11:32Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-86adeed75b2449c8acf634640b9894192022-12-22T03:55:57ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-03-011310.3389/fnmol.2020.00035513811Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's DiseaseAna F. Raimundo0Ana F. Raimundo1Ana F. Raimundo2Sofia Ferreira3Sofia Ferreira4Ivo C. Martins5Regina Menezes6Regina Menezes7Regina Menezes8iBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, PortugalCEDOC - Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, PortugalITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, PortugaliBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, PortugalCEDOC - Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, PortugalInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, PortugaliBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, PortugalCEDOC - Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, PortugalITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, PortugalDiabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It contributes to the maintenance of glucose physiological levels namely by inhibiting insulin and glucagon secretion as well as controlling adiposity and satiation. IAPP is a highly amyloidogenic polypeptide forming intracellular aggregates and amyloid structures that are associated with β-cell death. Data also suggest the relevance of unprocessed IAPP forms as seeding for amyloid buildup. Besides the known consequences of hyperamylinemia in the pancreas, evidence has also pointed out that IAPP has a pathological role in cognitive function. More specifically, IAPP was shown to impair the blood–brain barrier; it was also seen to interact and co-deposit with amyloid beta peptide (Aß), and possibly with Tau, within the brain of Alzheimer's disease (AD) patients, thereby contributing to diabetes-associated dementia. In fact, it has been suggested that AD results from a metabolic dysfunction in the brain, leading to its proposed designation as type 3 diabetes. Here, we have first provided a brief perspective on the IAPP amyloidogenic process and its role in diabetes and AD. We have then discussed the potential interventions for modulating IAPP proteotoxicity that can be explored for therapeutics. Finally, we have proposed the concept of a “diabetes brain phenotype” hypothesis in AD, which may help design future IAPP-centered drug developmentstrategies against AD.https://www.frontiersin.org/article/10.3389/fnmol.2020.00035/fullAß-42Alzheimer's diseaseamylindiabetesIAPPprotein aggregation |
| spellingShingle | Ana F. Raimundo Ana F. Raimundo Ana F. Raimundo Sofia Ferreira Sofia Ferreira Ivo C. Martins Regina Menezes Regina Menezes Regina Menezes Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease Frontiers in Molecular Neuroscience Aß-42 Alzheimer's disease amylin diabetes IAPP protein aggregation |
| title | Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease |
| title_full | Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease |
| title_fullStr | Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease |
| title_full_unstemmed | Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease |
| title_short | Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease |
| title_sort | islet amyloid polypeptide a partner in crime with aβ in the pathology of alzheimer s disease |
| topic | Aß-42 Alzheimer's disease amylin diabetes IAPP protein aggregation |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2020.00035/full |
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