PUBLICATION
Environment-Sensitive Probes for Illuminating Amyloid Aggregation in vitro and in Zebrafish
- Authors
- Fueyo-González, F., Gonzalez Vera, J.A., Alkorta, I., Infantes, L., Jimeno, M.L., Aranda, P., Acuña-Castroviejo, D., Ruiz-Arias, A., Orte, A., Herranz, R.
- ID
- ZDB-PUB-200620-3
- Date
- 2020
- Source
- ACS sensors 5(9): 2792-2799 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amyloid beta-Peptides*
- Amyloidogenic Proteins
- Animals
- Fluorescent Dyes
- Microscopy, Fluorescence
- Zebrafish*
- PubMed
- 32551591 Full text @ ACS Sens
Citation
Fueyo-González, F., Gonzalez Vera, J.A., Alkorta, I., Infantes, L., Jimeno, M.L., Aranda, P., Acuña-Castroviejo, D., Ruiz-Arias, A., Orte, A., Herranz, R. (2020) Environment-Sensitive Probes for Illuminating Amyloid Aggregation in vitro and in Zebrafish. ACS sensors. 5(9):2792-2799.
Abstract
The aberrant aggregation of certain peptides and proteins, forming extracellular plaques of fibrillar material is one of the hallmarks of amyloid disease, 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 on 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 pre-fibrillar aggregates. Among the different probes prepared, the 9-azetidinyl-quinolimide derivative showed striking performance in 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 a novel, multi-dimensional 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 MPTP. Our results support the potential of the novel fluorophores as powerful tools to follow amyloid aggregation using fluorescence microscopy in vivo, and revealing heterogeneous populations of different types of aggregates and, more broadly, to study protein interactions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping