FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors
Identifikátory výsledku
Kód výsledku v 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>
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30103 - Neurosciences (including psychophysiology)
Návaznosti výsledku
Projekt
—
Návaznosti
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2021
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Journal of Neurochemistry
ISSN
0022-3042
e-ISSN
—
Svazek periodika
159
Číslo periodika v rámci svazku
5
Stát vydavatele periodika
GB - Spojené království Velké Británie a Severního Irska
Počet stran výsledku
12
Strana od-do
901-912
Kód UT WoS článku
000715432700001
EID výsledku v databázi Scopus
2-s2.0-85118592475