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Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F22%3A00558474" target="_blank" >RIV/67985904:_____/22:00558474 - isvavai.cz</a>

  • Alternative codes found

    RIV/68378041:_____/22:00558474

  • Result on the web

    <a href="https://www.mdpi.com/1422-0067/23/10/5598" target="_blank" >https://www.mdpi.com/1422-0067/23/10/5598</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.3390/ijms23105598" target="_blank" >10.3390/ijms23105598</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma

  • Original language description

    Background: Huntington's disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients' plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a similar to 70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (p = 0.02). (4) Conclusions: Our study represents a valuable initial step towards the characterization of EV content in the search for HD biomarkers.

  • 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

    30103 - Neurosciences (including psychophysiology)

Result continuities

  • Project

    <a href="/en/project/GA19-01747S" target="_blank" >GA19-01747S: Proteomic analysis of extracellular vesicles in Huntington's disease</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2022

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    International Journal of Molecular Sciences

  • ISSN

    1422-0067

  • e-ISSN

    1422-0067

  • Volume of the periodical

    23

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    CH - SWITZERLAND

  • Number of pages

    20

  • Pages from-to

    5598

  • UT code for WoS article

    000803383400001

  • EID of the result in the Scopus database

    2-s2.0-85130180340