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PI3-kinase delta enhances axonalPIP(3)to support axon regeneration in the adultCNS

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F20%3A00540377" target="_blank" >RIV/68378041:_____/20:00540377 - isvavai.cz</a>

  • Result on the web

    <a href="https://www.embopress.org/doi/full/10.15252/emmm.201911674" target="_blank" >https://www.embopress.org/doi/full/10.15252/emmm.201911674</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.15252/emmm.201911674" target="_blank" >10.15252/emmm.201911674</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    PI3-kinase delta enhances axonalPIP(3)to support axon regeneration in the adultCNS

  • Original language description

    Peripheral nervous system (PNS) neurons support axon regeneration into adulthood, whereas central nervous system (CNS) neurons lose regenerative ability after development. To better understand this decline whilst aiming to improve regeneration, we focused on phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol (3,4,5)-trisphosphate (PIP3). We demonstrate that adultPNSneurons utilise two catalytic subunits ofPI3K for axon regeneration: p110 alpha and p110 delta. However, in theCNS, axonalPIP(3)decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110 alpha inCNSneurons had no effect, however, expression of p110 delta restored axonalPIP(3)and increased regenerative axon transport. p110 delta expression enhancedCNSregeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110 alpha. Furthermore, viral delivery of p110 delta promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonalPIP(3)as a key reason for intrinsic regeneration failure and demonstrate that native p110 delta facilitates axon regeneration by functioning in a hyperactive fashion.

  • 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/EF15_003%2F0000419" target="_blank" >EF15_003/0000419: Center of Reconstructive Neuroscience</a><br>

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2020

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    EMBO Molecular Medicine

  • ISSN

    1757-4684

  • e-ISSN

  • Volume of the periodical

    12

  • Issue of the periodical within the volume

    8

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    24

  • Pages from-to

    e11674

  • UT code for WoS article

    000561746100014

  • EID of the result in the Scopus database