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Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies
Baiping Ren1, Rundong Hu1, Mingzhen Zhang1
1Department of Chemical & Biomolecular Engineering, The University of Akron, Akron, OH, USA.
Alzheimer's and type 2 diabetes share links through protein interactions. This study provides methods to investigate how amyloid-beta and human islet amyloid polypeptide mixtures form aggregates and interact.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Alzheimer's disease (AD) and type 2 diabetes (T2D) are prevalent protein aggregation disorders.
- A potential link between AD and T2D involves cross-sequence interactions between amyloid-beta peptide (Aβ) and human islet amyloid polypeptide (hIAPP).
Purpose of the Study:
- To present experimental and computational protocols for studying Aβ-hIAPP mixtures.
- To investigate aggregate structures, kinetics, conformational conversion, and molecular interactions in these mixtures.
Main Methods:
- Utilized a combination of experimental and computational approaches.
- Developed protocols applicable to studying cross-seeding behaviors of amyloid peptides.
Main Results:
- Established protocols for analyzing Aβ-hIAPP interactions and aggregate formation.
- Provided tools to study the kinetics and structural conversions of mixed amyloid aggregates.
Conclusions:
- The presented protocols offer a framework for investigating the molecular mechanisms underlying the link between AD and T2D.
- These methods can be broadly applied to understand cross-seeding phenomena in other amyloidogenic diseases.
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