PMID- 37006768
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231101
IS  - 2691-3704 (Electronic)
IS  - 2691-3704 (Linking)
VI  - 3
IP  - 3
DP  - 2023 Mar 27
TI  - The Role of Heme and Copper in Alzheimer's Disease and Type 2 Diabetes Mellitus.
PG  - 657-681
LID - 10.1021/jacsau.2c00572 [doi]
AB  - Beyond the well-explored proposition of protein aggregation or amyloidosis as the 
      central event in amyloidogenic diseases like Alzheimer's Disease (AD), and Type 2 
      Diabetes Mellitus (T2Dm); there are alternative hypotheses, now becoming 
      increasingly evident, which suggest that the small biomolecules like redox 
      noninnocent metals (Fe, Cu, Zn, etc.) and cofactors (Heme) have a definite 
      influence in the onset and extent of such degenerative maladies. Dyshomeostasis 
      of these components remains as one of the common features in both AD and T2Dm 
      etiology. Recent advances in this course reveal that the metal/cofactor-peptide 
      interactions and covalent binding can alarmingly enhance and modify the toxic 
      reactivities, oxidize vital biomolecules, significantly contribute to the 
      oxidative stress leading to cell apoptosis, and may precede the amyloid fibrils 
      formation by altering their native folds. This perspective highlights this aspect 
      of amyloidogenic pathology which revolves around the impact of the metals and 
      cofactors in the pathogenic courses of AD and T2Dm including the active site 
      environments, altered reactivities, and the probable mechanisms involving some 
      highly reactive intermediates as well. It also discusses some in vitro metal 
      chelation or heme sequestration strategies which might serve as a possible 
      remedy. These findings might open up a new paradigm in our conventional 
      understanding of amyloidogenic diseases. Moreover, the interaction of the active 
      sites with small molecules elucidates potential biochemical reactivities that can 
      inspire designing of drug candidates for such pathologies.
CI  - (c) 2023 The Authors. Published by American Chemical Society.
FAU - Pal, Ishita
AU  - Pal I
AD  - School of Chemical Sciences, Indian Association for the Cultivation of Science, 
      2A & 2B, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
FAU - Dey, Somdatta Ghosh
AU  - Dey SG
AUID- ORCID: 0000-0002-6142-2202
AD  - School of Chemical Sciences, Indian Association for the Cultivation of Science, 
      2A & 2B, Raja S. C. Mullick Road, Jadavpur, Kolkata 700032, India.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230217
PL  - United States
TA  - JACS Au
JT  - JACS Au
JID - 101775714
PMC - PMC10052274
COIS- The authors declare no competing financial interest.
EDAT- 2023/04/04 06:00
MHDA- 2023/04/04 06:01
PMCR- 2023/02/17
CRDT- 2023/04/03 03:51
PHST- 2022/10/18 00:00 [received]
PHST- 2022/12/23 00:00 [revised]
PHST- 2022/12/23 00:00 [accepted]
PHST- 2023/04/04 06:01 [medline]
PHST- 2023/04/03 03:51 [entrez]
PHST- 2023/04/04 06:00 [pubmed]
PHST- 2023/02/17 00:00 [pmc-release]
AID - 10.1021/jacsau.2c00572 [doi]
PST - epublish
SO  - JACS Au. 2023 Feb 17;3(3):657-681. doi: 10.1021/jacsau.2c00572. eCollection 2023 
      Mar 27.