Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

Ana F. Raimundo, Sofia Ferreira, Ivo C. Martins, Regina Menezes

Research output: Contribution to journalReview article

4 Citations (Scopus)
9 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number35
JournalFrontiers in Molecular Neuroscience
Volume13
DOIs
Publication statusPublished - 20 Mar 2020

Keywords

  • Alzheimer's disease
  • amylin
  • Aß-42
  • diabetes
  • IAPP
  • protein aggregation

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