Screening Carbon Nano Materials for Preventing Amyloid Protein Aggregation by Adopting a Facile Method

• Published in: Cell biochemistry and biophysics 2024-06, Vol.82 (2), p.1389-1395
• Main Authors: Wilson, Daisy L., Carreon, Ana, Chinnam, Sampath, Sharifan, Hamidreza, Ahlawat, Jyoti, Narayan, Mahesh
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amylin; Amyloid - chemistry; Amyloid - metabolism; Amyloid beta-Peptides - chemistry; Amyloid beta-Peptides - metabolism; Amyloidogenesis; Amyloidogenic Proteins - chemistry; Amyloidogenic Proteins - metabolism; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Carbon - chemistry; Cell Biology; Diabetes mellitus (non-insulin dependent); Electrophoresis; Fibrils; Humans; Huntingtin; Huntington's disease; Huntingtons disease; Intermediates; Life Sciences; Monomers; Movement disorders; Neurodegenerative diseases; Oligomerization; Oligomers; Original Paper; Parkinson's disease; Pharmacology/Toxicology; Polypeptides; Protein Aggregates; Protein interaction; Proteins; Synuclein; β-Amyloid
• ISSN: 1085-9195; 1559-0283; 1559-0283
• DOI: 10.1007/s12013-024-01293-x

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aβ), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others are associated with disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates, including oligomers, continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively and quantitatively report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive, and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention. Graphical Abstract