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Diabetes Drug Discovery: hIAPP 1-37 Polymorphic Amyloid Structures as Novel Therapeutic Targets.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2018 Mar 19; Vol. 23 (3). Date of Electronic Publication: 2018 Mar 19. - Publication Year :
- 2018
-
Abstract
- Human islet amyloid peptide (hIAPP <subscript>1-37</subscript> ) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP <subscript>1-37</subscript> ) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP <subscript>1-37</subscript> aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP <subscript>1-37</subscript> . When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP <subscript>1-37</subscript> . Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP <subscript>1-37</subscript> oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A - F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities.<br />Competing Interests: The author declares having filled two patent applications WO2010118706 A2 and WO2014131374 A1.
- Subjects :
- Animals
Cell Survival drug effects
Cerebellum pathology
Curcumin chemistry
Curcumin therapeutic use
Diabetes Mellitus pathology
Humans
Islet Amyloid Polypeptide toxicity
Islet Amyloid Polypeptide ultrastructure
Kinetics
Mice
Molecular Docking Simulation
Protein Aggregates
Protein Folding
Protein Multimerization
Rats, Wistar
Amyloid chemistry
Diabetes Mellitus drug therapy
Drug Discovery
Islet Amyloid Polypeptide chemistry
Molecular Targeted Therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 23
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 29562662
- Full Text :
- https://doi.org/10.3390/molecules23030686