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Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F25%3A00082439" target="_blank" >RIV/00159816:_____/25:00082439 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14110/25:00143786

  • Result on the web

    <a href="https://pubs.acs.org/doi/10.1021/acs.chemrestox.4c00348" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.chemrestox.4c00348</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1021/acs.chemrestox.4c00348" target="_blank" >10.1021/acs.chemrestox.4c00348</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress

  • Original language description

    Malondialdehyde (MDA), a major reactive byproduct of lipid peroxidation, has been implicated in numerous pathological conditions as a result of altering the structure and function of crucial proteins. One such protein is alpha-synuclein (alpha-Syn), which plays a vital role in the pathogenesis of Parkinson&apos;s disease (PD). This study investigates the hypothesis that MDA causes structural alterations in alpha-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified alpha-Syn were injected to the brain of mice. Behavioral assessments were performed to evaluate motor function changes, while immunohistochemistry was employed to examine the extent of alpha-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified alpha-Syn from brain tissue. Moreover, 15Nitrogen-labeled alpha-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in alpha-Syn alter its structural properties and also significantly enhance its aggregation propensity, potentially contributing to the neurodegenerative processes observed in PD. The developed model displayed a nonreversible decline in motor function, neurodegeneration, and aggregation of proteins in the brain mimicking the PD conditions. This research provides valuable insights into the molecular mechanisms of PD, emphasizing the role of MDA-modified proteins in the etiology of PD.

  • 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

    30105 - Physiology (including cytology)

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2025

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    CHEMICAL RESEARCH IN TOXICOLOGY

  • ISSN

    0893-228X

  • e-ISSN

    1520-5010

  • Volume of the periodical

    38

  • Issue of the periodical within the volume

    4

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    10

  • Pages from-to

    573-582

  • UT code for WoS article

    001461031900001

  • EID of the result in the Scopus database