中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (6): 1127-1130.doi: 10.4103/1673-5374.300323

• 综述:退行性病与再生 • 上一篇    下一篇

胰岛淀粉样多肽和β淀粉样肽在阿尔茨海默病中的作用:两种诱因,一种疾病

  

  • 出版日期:2021-06-15 发布日期:2020-12-31

Islet amyloid polypeptide & amyloid beta peptide roles in Alzheimer’s disease: two triggers, one disease

Sofia Ferreira1, 2, #, Ana F. Raimundo1, 2, 3, #, Regina Menezes1, 2, 3, *, Ivo C. Martins4, *   

  1. 1 iBET - Instituto de Biologia Experimental e Tecnológica, Oeiras, Portugal;  2 CEDOC - Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal;  3 ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal;  4 Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal 
  • Online:2021-06-15 Published:2020-12-31
  • Contact: Regina Menezes, PhD, rmenezes@ibet.pt, regina.menezes@nms.unl.pt; Ivo C. Martins, PhD, ivomartins@medicina.ulisboa.pt.
  • Supported by:
    This work was supported by iNOVA4Health – UID/Multi/04462/2019, a program financially supported by Fundação para a Ciência e Tecnologia/ Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, Funding from INTERFACE Programme, through the Innovation, Technology and Circular Economy Fund (FITEC), FCT via PTDC/BIA-MOL/31104/2017 and UID/Multi/04462/2019-SubProj iNOVA4Health C44 (to RM), PD/BD/135504/2018 (to AFR), Sociedade Portuguesa de Diabetologia for the Nuno Castelo-Branco Prize – 2016 (to RM), and ICM acknowledges FCT-MCTES Program “Concurso de Estímulo ao Emprego Científico” (CEECIND/01670/2017).

摘要:

https://orcid.org/0000-0002-9284-8599 (Ivo C. Martins); 

https://orcid.org/0000-0003-0552-8480 (Regina Menezes); 

https://orcid.org/0000-0002-3582-3504 (Ana F. Raimundo); 

https://orcid.org/0000-0002-0752-8938 (Sofia Ferreira) 

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions worldwide. Due to population ageing, the incidence of AD is increasing. AD patients develop cognitive decline and dementia, features for which is known, requiring permanent care. This poses a major socio-economic burden on healthcare systems as AD patients’ relatives and healthcare workers are forced to cope with rising numbers of affected people. Despite recent advances, AD pathological mechanisms are not fully understood. Nevertheless, it is clear that the amyloid beta (Aβ) peptide, which forms amyloid plaques in AD patients’ brains, plays a key role. Type 2 diabetes, the most common form of diabetes, affects hundreds of million people globally. Islet amyloid polypeptide (IAPP) is a hormone co-produced and secreted with insulin in pancreatic β-cells, with a key role in diabetes, as it helps regulate glucose levels and control adiposity and satiation. Similarly to Aβ, IAPP is very amyloidogenic, generating intracellular amyloid deposits that cause β-cell dysfunction and death. It is now clear that IAPP can also have a pathological role in AD, decreasing cognitive function. IAPP harms the blood-brain barrier, directly interacts and co-deposits with Aβ, promoting diabetes-associated dementia. IAPP can cause a metabolic dysfunction in the brain, leading to other diabetes-related forms of AD. Thus, here we discuss IAPP association with diabetes, Aβ and dementia, in the context of what we designate a “diabetes brain phenotype” AD hypothesis. Such approach helps to set a conceptual framework for future IAPP-based drugs against AD. 

Key words: aggregation, Alzheimer, amylin, amyloid, diabetes, islet amyloid polypeptide