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alpha-Synuclein aggregation at low concentrations

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10395403" target="_blank" >RIV/00216208:11310/19:10395403 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11320/19:10395403

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=30KncdIFRk" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=30KncdIFRk</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>

Alternative languages

  • Result language

    angličtina

  • Original language name

    alpha-Synuclein aggregation at low concentrations

  • Original language description

    Background: Aggregation of the neuronal protein alpha-synuclein into amyloid fibrils is a hallmark of Parkinson&apos;s disease. The propensity of alpha-synuclein to aggregate increases with the protein concentration. For the development of efficient inhibitors of alpha-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 alpha-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 alpha-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 alpha-synuclein solutions of high concentrations. Conclusions: The critical concentration of a-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 alpha-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 alpha-synuclein at low micromolar concentration.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10608 - Biochemistry and molecular biology

Result continuities

  • Project

    <a href="/en/project/ED4.1.00%2F16.0340" target="_blank" >ED4.1.00/16.0340: Upgrade of facilities for physical research and education</a><br>

  • Continuities

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

Others

  • Publication year

    2019

  • Confidentiality

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

Data specific for result type

  • 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