PMID- 31333136
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20200914
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 20
IP  - 16
DP  - 2019
TI  - Computational and Experimental Approaches to Design Inhibitors of Amylin 
      Aggregation.
PG  - 1680-1694
LID - 10.2174/1389450120666190719164316 [doi]
AB  - Amylin is a neuroendocrine peptide hormone secreted by pancreatic ss-cells; 
      however, amylin is toxic to ss-cells when it is aggregated in type 2 diabetes 
      mellitus (T2DM). It is important to understand amylin's structures and 
      aggregation mechanism for the discovery and design of effective drugs to inhibit 
      amylin aggregation. In this review, we investigated experimental and 
      computational studies on amylin structures and inhibitors. Our review provides 
      some novel insights into amylin, particularly for the design of its aggregation 
      inhibitors to treat T2DM. We detailed the potential inhibitors that have been 
      studied hitherto and highlighted the neglected need to consider different amylin 
      attributes that depend on the presence/absence of physiologically relevant 
      conditions, such as membranes. These conditions and the experimental methods can 
      greatly influence the results of studies on amylininhibitor complexes. 
      Text-mining over 3,000 amylin-related PubMed abstracts suggests the combined 
      therapeutic potential of amylin with leptin and glucagon-like peptide-1, which 
      are two key hormones in obesity. The results also suggest that targeting amylin 
      aggregation can contribute to therapeutic efforts for Alzheimer's disease (AD). 
      Therefore, we have also reviewed the role of amylin in other conditions including 
      obesity and AD. Finally, we provided insights for designing inhibitors of 
      different types (small molecules, proteins, peptides/mimetics, metal ions) to 
      inhibit amylin aggregation.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Kumar, Ammu Prasanna
AU  - Kumar AP
AD  - Department of Chemistry, College of Arts and Sciences, Khalifa University, Abu 
      Dhabi, United Arab Emirates.
AD  - Research Unit in Bioinformatics, Department of Biochemistry and Microbiology, 
      Rhodes University, South Africa.
FAU - Lee, Sungmun
AU  - Lee S
AD  - Department of Biomedical Engineering and Healthcare Engineering Innovation 
      Center, College of Engineering, Khalifa University, Abu Dhabi, United Arab 
      Emirates.
FAU - Lukman, Suryani
AU  - Lukman S
AD  - Department of Chemistry, College of Arts and Sciences, Khalifa University, Abu 
      Dhabi, United Arab Emirates.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Peptide Hormones)
RN  - 0 (Protein Aggregates)
SB  - IM
MH  - Alzheimer Disease/drug therapy/metabolism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Humans
MH  - Islet Amyloid Polypeptide/*metabolism
MH  - Peptide Hormones/metabolism
MH  - Protein Aggregates/*drug effects
OTO - NOTNLM
OT  - Alzheimer's disease therapy
OT  - Amylin
OT  - IAPP
OT  - aggregation inhibitors
OT  - conformation of amylin
OT  - islet amyloid polypeptide
OT  - literature review
OT  - type 2 diabetes therapy.
EDAT- 2019/07/25 06:00
MHDA- 2020/09/15 06:00
CRDT- 2019/07/24 06:00
PHST- 2019/04/30 00:00 [received]
PHST- 2019/07/04 00:00 [revised]
PHST- 2019/07/05 00:00 [accepted]
PHST- 2019/07/25 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
PHST- 2019/07/24 06:00 [entrez]
AID - CDT-EPUB-99790 [pii]
AID - 10.2174/1389450120666190719164316 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2019;20(16):1680-1694. doi: 10.2174/1389450120666190719164316.