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Thiophene‐Based Optical Ligands That Selectively Detect Aβ Pathology in Alzheimer's Disease

In several neurodegenerative diseases, the presence of aggregates of specific proteins in the brain is a significant pathological hallmark; thus, developing ligands able to bind to the aggregated proteins is essential for any effort related to imaging and therapeutics. Here we report the synthesis o...

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Detalles Bibliográficos
Autores principales: Klingstedt, Therése, Shirani, Hamid, Ghetti, Bernardino, Vidal, Ruben, R. Nilsson, K. Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409278/
https://www.ncbi.nlm.nih.gov/pubmed/34101954
http://dx.doi.org/10.1002/cbic.202100199
Descripción
Sumario:In several neurodegenerative diseases, the presence of aggregates of specific proteins in the brain is a significant pathological hallmark; thus, developing ligands able to bind to the aggregated proteins is essential for any effort related to imaging and therapeutics. Here we report the synthesis of thiophene‐based ligands containing nitrogen heterocycles. The ligands selectively recognized amyloid‐β (Aβ) aggregates in brain tissue from individuals diagnosed neuropathologically as having Alzheimer's disease (AD). The selectivity for Aβ was dependent on the position of nitrogen in the heterocyclic compounds, and the ability to bind Aβ was shown to be reduced when introducing anionic substituents on the thiophene backbone. Our findings provide the structural and functional basis for the development of ligands that can differentiate between aggregated proteinaceous species comprised of distinct proteins. These ligands might also be powerful tools for studying the pathogenesis of Aβ aggregation and for designing molecules for imaging of Aβ pathology.