α-Synuclein aggregation at low concentrations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00507378" target="_blank" >RIV/61388963:_____/19:00507378 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/abs/pii/S1570963919300834?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/abs/pii/S1570963919300834?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bbapap.2019.05.003" target="_blank" >10.1016/j.bbapap.2019.05.003</a>

Result language

angličtina

Original language name

α-Synuclein aggregation at low concentrations

Original language description

Background: Aggregation of the neuronal protein α-synuclein into amyloid fibrils is a hallmark of Parkinson's disease. The propensity of α-synuclein to aggregate increases with the protein concentration. For the development of efficient inhibitors of α-synuclein aggregation, it is important to know the critical concentration of aggregation (the concentration of monomeric protein, below which the protein does not aggregate). Methods: We performed in vitro aggregation studies of α-synuclein at low concentrations (0.11-20 mu M). Aggregation kinetics was measured by ThT fluorescence. Obtained aggregates were characterized using CD-spectroscopy, fluorescent spectroscopy, dynamic light scattering and AFM imaging. Results: Monomeric α-synuclein at concentrations 0.45 mu M and above was able to bind to fibril ends resulting in fibril growth. At the protein concentrations below 0.4 mu M, monomers did not fibrillize, and fibrils disaggregated. In the absence of seeds, fibrils were formed only at monomer concentrations higher than 10 mu M. At low micromolar concentrations, we observed formation of prefibrillar amyloid aggregates, which are able to induce fibril formation in α-synuclein solutions of high concentrations. Conclusions: The critical concentration of α-synuclein fibril growth is similar to 0.4 mu M. Prefibrillar amyloid aggregates appear at concentrations between 0.45 and 3 mu M and are an intermediate state between monomers and fibrils. Although morphologically different from fibrils, prefibrillar aggregates have similar properties to those of fibrils. General significance: We determined the critical concentration of α-synuclein fibril growth. We showed that fibrils can grow at much lower monomer concentrations than that required for de novo fibril formation. We characterized a prefibrillar intermediate species formed upon aggregation of α-synuclein at low micromolar concentration.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

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

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Biochimica Et Biophysica Acta-Proteins and Proteomics

ISSN

1570-9639

e-ISSN

—

Volume of the periodical

1867

Issue of the periodical within the volume

7/8

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

701-709

UT code for WoS article

000472814000003

EID of the result in the Scopus database

2-s2.0-85065874149