PMID- 34119687
OWN - NLM
STAT- MEDLINE
DCOM- 20210910
LR  - 20210910
IS  - 1872-9649 (Electronic)
IS  - 1568-1637 (Linking)
VI  - 70
DP  - 2021 Sep
TI  - Living with the enemy: from protein-misfolding pathologies we know, to those we 
      want to know.
PG  - 101391
LID - S1568-1637(21)00138-0 [pii]
LID - 10.1016/j.arr.2021.101391 [doi]
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.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Emwas, Abdul-Hamid
AU  - Emwas AH
AD  - King Abdullah University of Science and Technology, Core Labs, Thuwal, 
      23955-6900, Saudi Arabia.
FAU - Alghrably, Mawadda
AU  - Alghrably M
AD  - King Abdullah University of Science and Technology (KAUST), Biological and 
      Environmental Sciences & Engineering Division (BESE), Thuwal, 23955-6900, Saudi 
      Arabia.
FAU - Dhahri, Manel
AU  - Dhahri M
AD  - Biology Department, Faculty of Science Yanbu, Taibah University, 46423, Yanbu 
      El-Bahr, Saudi Arabia.
FAU - Sharfalddin, Abeer
AU  - Sharfalddin A
AD  - Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 
      80203, Jeddah, 21589, Saudi Arabia.
FAU - Alsiary, Rawiah
AU  - Alsiary R
AD  - King Abdullah International Medical Research Center/King Saud bin Abdulaziz 
      University for Health Sciences, Western Region-Hospital-MNGHA, Saudi Arabia.
FAU - Jaremko, Mariusz
AU  - Jaremko M
AD  - King Abdullah University of Science and Technology (KAUST), Biological and 
      Environmental Sciences & Engineering Division (BESE), Thuwal, 23955-6900, Saudi 
      Arabia. Electronic address: Mariusz.jaremko@kaust.edu.sa.
FAU - Faa, Gavino
AU  - Faa G
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Campagna, Marcello
AU  - Campagna M
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Congiu, Terenzio
AU  - Congiu T
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Piras, Monica
AU  - Piras M
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Piludu, Marco
AU  - Piludu M
AD  - Department of Biomedical Sciences, Universita di Cagliari, Cittadella 
      Universitaria, 09042, Monserrato, Italy.
FAU - Pichiri, Giuseppina
AU  - Pichiri G
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Coni, Pierpaolo
AU  - Coni P
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy.
FAU - Lachowicz, Joanna Izabela
AU  - Lachowicz JI
AD  - Department of Medical Sciences and Public Health, Universita di Cagliari, 
      Cittadella Universitaria, 09042, Monserrato, Italy. Electronic address: 
      lachowicz@unica.it.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210611
PL  - England
TA  - Ageing Res Rev
JT  - Ageing research reviews
JID - 101128963
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Islet Amyloid Polypeptide)
SB  - IM
MH  - Amyloid beta-Peptides
MH  - *Diabetes Mellitus, Type 2
MH  - Humans
MH  - Islet Amyloid Polypeptide
MH  - *Parkinson Disease
MH  - *alpha 1-Antitrypsin Deficiency
OTO - NOTNLM
OT  - Tau protein (Tau)
OT  - alpha-1 antitrypsin (AAT)
OT  - alpha-synuclein (alpha-S)
OT  - amyloid beta (Abeta)
OT  - diabetes
OT  - human islet amyloid polypeptide (hIAPP)
OT  - metal binding
OT  - neurodegeneration
EDAT- 2021/06/14 06:00
MHDA- 2021/09/11 06:00
CRDT- 2021/06/13 20:42
PHST- 2021/02/18 00:00 [received]
PHST- 2021/04/19 00:00 [revised]
PHST- 2021/06/09 00:00 [accepted]
PHST- 2021/06/14 06:00 [pubmed]
PHST- 2021/09/11 06:00 [medline]
PHST- 2021/06/13 20:42 [entrez]
AID - S1568-1637(21)00138-0 [pii]
AID - 10.1016/j.arr.2021.101391 [doi]
PST - ppublish
SO  - Ageing Res Rev. 2021 Sep;70:101391. doi: 10.1016/j.arr.2021.101391. Epub 2021 Jun 
      11.