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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00548774" target="_blank" >RIV/61388963:_____/21:00548774 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1111/jnc.15528" target="_blank" >https://doi.org/10.1111/jnc.15528</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jnc.15528" target="_blank" >10.1111/jnc.15528</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

Aggregation of small neuronal protein α-synuclein (αSyn) 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 αSyn 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 αSyn aggregation inhibitors in cells that is based on fluorescence resonance energy transfer (FRET) between labeled αSyn molecules in fibrils. The assay directly reports the amount of fibrillized αSyn 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 αSyn. The developed FRET-based assay does not interfere with the aggregation process and is suitable for high-throughput testing of αSyn 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 α-synuclein aggregation inhibitors

Popis výsledku anglicky

Aggregation of small neuronal protein α-synuclein (αSyn) 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 αSyn 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 αSyn aggregation inhibitors in cells that is based on fluorescence resonance energy transfer (FRET) between labeled αSyn molecules in fibrils. The assay directly reports the amount of fibrillized αSyn 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 αSyn. The developed FRET-based assay does not interfere with the aggregation process and is suitable for high-throughput testing of αSyn aggregation inhibitors. Its application can sort out non-specific inhibitors and thus significantly facilitate the development of drugs for Parkinson`s disease.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10610 - Biophysics

Projekt

<a href="/cs/project/GJ18-06255Y" target="_blank" >GJ18-06255Y: Nová strategie pro inhibici tvorby amyloidních fibril</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Neurochemistry

ISSN

0022-3042

e-ISSN

1471-4159

Svazek periodika

159

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

901-912

Kód UT WoS článku

000715432700001

EID výsledku v databázi Scopus

2-s2.0-85118592475