TY - JOUR
T1 - Living with the enemy: from protein-misfolding pathologies we know, to those we want to know
AU - Emwas, Abdul-Hamid
AU - Alghrably, Mawadda
AU - Dhahri, Manel
AU - Sharfalddin, Abeer
AU - Alsiary, Rawiah
AU - Jaremko, Mariusz
AU - Faa, Gavino
AU - Campagna, Marcello
AU - Congiu, Terenzio
AU - Piras, Monica
AU - Piludu, Marco
AU - Pichiri, Giuseppina
AU - Coni, Pierpaolo
AU - lachowicz, joanna izabela
N1 - KAUST Repository Item: Exported on 2021-06-15
PY - 2021/6/11
Y1 - 2021/6/11
N2 - 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.
AB - 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.
UR - http://hdl.handle.net/10754/669568
UR - https://linkinghub.elsevier.com/retrieve/pii/S1568163721001380
U2 - 10.1016/j.arr.2021.101391
DO - 10.1016/j.arr.2021.101391
M3 - Article
C2 - 34119687
SN - 1568-1637
VL - 70
SP - 101391
JO - Ageing Research Reviews
JF - Ageing Research Reviews
ER -
