Alpha-Synuclein Aggregation Mechanism in the Presence of Nanomaterials

Malik, SA and Mondal, S and Atreya, HS (2023) Alpha-Synuclein Aggregation Mechanism in the Presence of Nanomaterials. In: Biochemistry .

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Abstract

Parkinson�s disease (PD) is characterized by the toxic oligomeric and fibrillar phases formed by monomeric alpha-synuclein (α-syn). Certain nanoparticles have been demonstrated to promote protein aggregation, while other nanomaterials have been found to prevent the process. In the current work, we use nuclear magnetic resonance spectroscopy in conjunction with isothermal titration calorimetry to investigate the cause and mechanism of these opposing effects at the amino acid protein level. The interaction of α-syn with two types of nanomaterials was considered: citrate-capped gold nanoparticles (AuNPs) and graphene oxide (GO). In the presence of AuNPs, α-syn aggregation is accelerated, whereas in the presence of GO, aggregation is prevented. The study indicates that GO sequesters the NAC region of α-syn monomers through electrostatic and hydrophobic interactions, leading to a reduced elongation rate, and AuNPs leave the NAC region exposed while binding the N-terminus, leading to higher aggregation. The protein�s inclination toward quicker aggregation is explained by the binding of the N-terminus of α-syn with the gold nanoparticles. Conversely, a comparatively stronger interaction with GO causes the nucleation and growth phases to be postponed and inhibits intermolecular interactions. Our finding offers novel experimental insights at the residue level regarding the aggregation of α-syn in the presence of various nanomaterials and creates new opportunities for the development of suitably functionalized nanomaterial-based therapeutic reagents against Parkinson�s and other neurodegenerative diseases. © 2024 American Chemical Society.

Item Type:	Journal Article
Publication:	Biochemistry
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Keywords:	Fiber optic sensors; Gold compounds; Gold nanoparticles; Graphene; Hydrophobicity; Metal nanoparticles; Neurodegenerative diseases; Nuclear magnetic resonance spectroscopy; Proteins, 'current; Aggregation mechanism; Fibrillar phase; Gold nanoparticle; Gold Nanoparticles; Graphene oxides; Monomerics; N terminus; Protein aggregation; Synuclein, Agglomeration, alpha synuclein; citric acid; gold; graphene oxide; graphite; metal nanoparticle; nanomaterial; protein aggregate; SNCA protein, human, chemical phenomena; chemistry; drug effect; human; metabolism; Parkinson disease, alpha-Synuclein; Citric Acid; Gold; Graphite; Humans; Hydrophobic and Hydrophilic Interactions; Metal Nanoparticles; Nanostructures; Parkinson Disease; Protein Aggregates
Department/Centre:	Division of Chemical Sciences > Solid State & Structural Chemistry Unit
Date Deposited:	22 May 2024 11:57
Last Modified:	22 May 2024 11:57
URI:	https://eprints.iisc.ac.in/id/eprint/85079

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