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β-Carotene, a Potent Amyloid Aggregation Inhibitor, Promotes Disordered Aβ Fibrillar Structure

The aggregation of amyloid beta (Aβ) into fibrillar aggregates is a key feature of Alzheimer’s disease (AD) pathology. β-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of β-ca...

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Detalles Bibliográficos
Autores principales: Banerjee, Siddhartha, Baghel, Divya, Pacheco de Oliveira, Ana, Ghosh, Ayanjeet
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10049578/
https://www.ncbi.nlm.nih.gov/pubmed/36982248
http://dx.doi.org/10.3390/ijms24065175
Descripción
Sumario:The aggregation of amyloid beta (Aβ) into fibrillar aggregates is a key feature of Alzheimer’s disease (AD) pathology. β-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of β-carotene on the structure of amyloid aggregates is not known, which poses a limitation towards developing it as a potential AD therapeutic. In this report, we use nanoscale AFM-IR spectroscopy to probe the structure of Aβ oligomers and fibrils at the single aggregate level and demonstrate that the main effect of β-carotene towards modulating Aβ aggregation is not to inhibit fibril formation but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.