Inhibition of alpha-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00490459" target="_blank" >RIV/61388963:_____/18:00490459 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1002/anie.201801071" target="_blank" >http://dx.doi.org/10.1002/anie.201801071</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/anie.201801071" target="_blank" >10.1002/anie.201801071</a>

Result language

angličtina

Original language name

Inhibition of alpha-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends

Original language description

Misfolding of the protein alpha-synuclein (alpha Syn) into amyloid fibrils plays a central role in the development of Parkinson's disease. Most approaches for the inhibition of alpha Syn fibril formation are based on stabilizing the native monomeric form of the protein or destabilizing the fibrillized misfolded form. They require high concentrations of inhibitor and therefore cannot be easily used for therapies. In this work, we designed an inhibitor (Inh-beta) that selectively binds the growing ends of alpha Syn fibrils and creates steric hindrance for the binding of monomeric alpha Syn. This approach permits the inhibition of fibril formation at Inh-beta concentrations (IC50=850nm) much lower than the concentration of monomeric alpha Syn. We studied its kinetic mechanism invitro and identified the reactions that limit inhibition efficiency. It is shown that blocking of alpha Syn fibril ends is an effective approach to inhibiting fibril growth and provides insights for the development of effective inhibitors of alpha Syn aggregation.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10610 - Biophysics

Project

<a href="/en/project/GJ18-06255Y" target="_blank" >GJ18-06255Y: New strategy for inhibition of amyloid fibril formation</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

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

Name of the periodical

Angewandte Chemie - International Edition

ISSN

1433-7851

e-ISSN

—

Volume of the periodical

57

Issue of the periodical within the volume

20

Country of publishing house

DE - GERMANY

Number of pages

5

Pages from-to

5690-5694

UT code for WoS article

000431488200017

EID of the result in the Scopus database

2-s2.0-85045376750