FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F21%3A10441790" target="_blank" >RIV/00216208:11310/21:10441790 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kIrSw.71eZ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=kIrSw.71eZ</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/jnc.15528" target="_blank" >10.1111/jnc.15528</a>

Result language
angličtina
Original language name
FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors
Original language description
Aggregation of small neuronal protein alpha-synuclein (alpha Syn) in amyloid fibrils is considered to be one of the main causes of Parkinson's disease. Inhibition of this aggregation is a promising approach for disease treatment. Dozens of compounds able to inhibit alpha Syn fibrillization in solution were developed during the last decade. However, the applicability of most of them in the cellular environment was not established because of the absence of a suitable cell-based assay. In this work, we developed an assay for testing alpha Syn aggregation inhibitors in cells that is based on fluorescence resonance energy transfer (FRET) between labeled alpha Syn molecules in fibrils. The assay directly reports the amount of fibrillized alpha Syn and is more reliable than the assays based on cell viability. Moreover, we showed that cell viability decline does not always correlate with the amount of misfolded alpha Syn. The developed FRET-based assay does not interfere with the aggregation process and is suitable for high-throughput testing of alpha Syn aggregation inhibitors. Its application can sort out non-specific inhibitors and thus significantly facilitate the development of drugs for Parkinson's disease.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)

Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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