Environment-Sensitive Probes for Illuminating Amyloid Aggregation In Vitro and in Zebrafish
Abstract
The aberrant aggregation of certain peptides and proteins, forming extracellular plaques of fibrillar material, is one of the hallmarks of amyloid diseases, such as Alzheimer's and Parkinson's. Herein, we have designed a new family of solvatochromic dyes based on the 9-amino-quinolimide moiety capable of reporting during the early stages of amyloid fibrillization. We have rationally improved the photophysical properties of quinolimides by placing diverse amino groups at the 9-position of the quinolimide core, leading to higher solvatochromic and fluorogenic character and higher lifetime dependence on the hydrophobicity of the environment, which represent excellent properties for the sensitive detection of prefibrillar aggregates. Among the different probes prepared, the 9-azetidinyl-quinolimide derivative showed striking performance in the following β-amyloid peptide (Aβ) aggregation in solution in real time and identifying the formation of different types of early oligomers of Aβ, the most important species linked to cytotoxicity, using novel, multidimensional fluorescence microscopy, with one- or two-photon excitation. Interestingly, the new dye allowed the visualization of proteinaceous inclusion bodies in a zebrafish model with neuronal damage induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Our results support the potential of the novel fluorophores as powerful tools to follow amyloid aggregation using fluorescence microscopy in vivo, revealing heterogeneous populations of different types of aggregates and, more broadly, to study protein interactions.
Keywords: amyloid aggregation; environment-sensitive probes; fluorescent probes; quinolimide derivatives; ratiometric fluorescence lifetime imaging microscopy; two-photon excitation imaging; zebrafish imaging; β-amyloid peptide aggregation sensing.
This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32551591/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.
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