Living with the enemy: from protein-misfolding pathologies we know, to those we want to know.
Tau protein (Tau)
alpha-1 antitrypsin (AAT)
alpha-synuclein (α-S)
amyloid beta (Aβ)
diabetes
human islet amyloid polypeptide (hIAPP)
metal binding
neurodegeneration
Journal
Ageing research reviews
ISSN: 1872-9649
Titre abrégé: Ageing Res Rev
Pays: England
ID NLM: 101128963
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
18
02
2021
revised:
19
04
2021
accepted:
09
06
2021
pubmed:
14
6
2021
medline:
11
9
2021
entrez:
13
6
2021
Statut:
ppublish
Résumé
Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively.
Identifiants
pubmed: 34119687
pii: S1568-1637(21)00138-0
doi: 10.1016/j.arr.2021.101391
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Islet Amyloid Polypeptide
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101391Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.