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Small molecule-based fluorescent probes for the detection of α-Synuclein aggregation states. | LitMetric

Small molecule-based fluorescent probes for the detection of α-Synuclein aggregation states.

Bioorg Med Chem Lett

Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

Published: April 2023

AI Article Synopsis

Article Abstract

The formation of aggregates due to protein misfolding is encountered in various neurodegenerative diseases. α-Synuclein (α-Syn) aggregation is linked to Parkinson's disease (PD). It is one of the most prevalent neurodegenerative disorders after Alzheimer's disease. Aggregation of α-Syn is associated with Lewy body formation and degeneration of the dopaminergic neurons in the brain. These are the pathological hallmarks of PD progression. α-Syn aggregates in a multi-step process. The native unstructured α-Syn monomers combine to form oligomers, followed by amyloid fibrils, and finally Lewy bodies. Recent evidence suggests that α-Syn oligomerization and fibrils formation play major roles in PD development. α-Syn oligomeric species is the main contributor to neurotoxicity. Therefore, the detection of α-Syn oligomers and fibrils has drawn significant attention for potential diagnostic and therapeutic development. In this regard, the fluorescence strategy has become the most popular approach for following the protein aggregation process. Thioflavin T (ThT) is the most frequently used probe for monitoring amyloid kinetics. Unfortunately, it suffers from several significant drawbacks including the inability to detect neurotoxic oligomers. Researchers developed several small molecule-based advanced fluorescent probes compared to ThT for the detection/monitoring of α-Syn aggregates states. These are summarized here.

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Source
http://dx.doi.org/10.1016/j.bmcl.2023.129257DOI Listing

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