Thiophene-Based Ligands for Histological Multiplex Spectral Detection of Distinct Protein Aggregates in Alzheimer's Disease.
Thiophene-Based Ligands for Histological Multiplex Spectral Detection of Distinct Protein Aggregates in Alzheimer's Disease.
复制标题
用于阿尔茨海默病中不同蛋白质聚集体的组织学多重光谱检测的基于噻吩的配体。
DOI：
10.1002/chem.202203568
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nilsson,KPeterR
中科院分区：
文献类型：
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作者：
Lantz,Linda;Shirani,Hamid;Ghetti,Bernardino;Vidal,Ruben;Klingstedt,Therése;Nilsson,KPeterR
The aggregation and accumulation of proteins in the brain is the defining feature of many devastating neurodegenerative diseases. The development of fluorescent ligands that bind to these accumulations, or deposits, is essential for the characterization of these neuropathological lesions. We report the synthesis of donor‐acceptor‐donor (D‐A‐D) thiophene‐based ligands with different emission properties. The D‐A‐D ligands displayed selectivity towards distinct disease‐associated protein deposits in histological sections from postmortem brain tissue of individuals affected by Alzheimer's disease (AD). The ability of the ligands to selectively identify AD‐associated pathological alterations, such as deposits composed of aggregates of the amyloid‐β (Aβ) peptide or tau, was reduced when the chemical composition of the ligands was altered. When combining the D‐A‐D ligands with conventional thiophene‐based ligands, superior spectral separation of distinct protein aggregates in AD tissue sections was obtained. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species, as well as offer novel strategies for developing multiplex fluorescence detection of protein aggregates in tissue sections.
