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
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
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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
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