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Autor
Barber, Amanda C 1 Cave, Joshua 1 Conceicao, Raquel 1 Deshpande, Sarita S 1 Eickholt, Britta J 1 Eva, Richard 1 Evans, Rachel S 1 Fawcett, James W 1 Ffrench-Constant, Charles 1 Fuchs, Joachim 1 Haenzi, Barbara 1 Hulshof, Lianne A 1 Khatib, Tasneem Z 1 MacQueen, Amy R 1 Martin, Keith R 1 Nieuwenhuis, Bart 1 Okkenhaug, Klaus 1 Osborne, Andrew 1 Pearson, Craig S 1 Smith, Patrice D 1
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Pracoviště
Centre for Eye Research Australia Roy... 1 Centre of Reconstructive Neuroscience... 1 Department of Neuroscience Carleton U... 1 Department of Pathology University of... 1 Institute of Biochemistry Charité Uni... 1 John Van Geest Centre for Brain Repai... 1 Laboratory for Regeneration of Sensor... 1 Laboratory of Lymphocyte Signalling a... 1 MRC Centre for Regenerative Medicine ... 1 Ophthalmology Department of Surgery U... 1
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Autor
Barber, Amanda C 1 Cave, Joshua 1 Conceicao, Raquel 1 Deshpande, Sarita S 1 Eickholt, Britta J 1 Eva, Richard 1 Evans, Rachel S 1 Fawcett, James W 1 Ffrench-Constant, Charles 1 Fuchs, Joachim 1 Haenzi, Barbara 1 Hulshof, Lianne A 1 Khatib, Tasneem Z 1 MacQueen, Amy R 1 Martin, Keith R 1 Nieuwenhuis, Bart 1 Okkenhaug, Klaus 1 Osborne, Andrew 1 Pearson, Craig S 1 Smith, Patrice D 1
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Pracoviště
Centre for Eye Research Australia Roy... 1 Centre of Reconstructive Neuroscience... 1 Department of Neuroscience Carleton U... 1 Department of Pathology University of... 1 Institute of Biochemistry Charité Uni... 1 John Van Geest Centre for Brain Repai... 1 Laboratory for Regeneration of Sensor... 1 Laboratory of Lymphocyte Signalling a... 1 MRC Centre for Regenerative Medicine ... 1 Ophthalmology Department of Surgery U... 1
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Nieuwenhuis, Bart
Autor Nieuwenhuis, Bart John Van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK Laboratory for Regeneration of Sensorimotor Systems, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, The Netherlands
- Barber, Amanda C
- Evans, Rachel S
- Pearson, Craig S
- Fuchs, Joachim
- MacQueen, Amy R
- van Erp, Susan
- Haenzi, Barbara
- Hulshof, Lianne A
- Osborne, Andrew
Free Medical Journals od 2009
PubMed Central od 2009
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Open Access Digital Library od 2009-01-01
Open Access Digital Library od 2009-01-01
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PubMed
32558386
DOI
10.15252/emmm.201911674
Knihovny.cz E-zdroje
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 adult PNS neurons utilise two catalytic subunits of PI3K for axon regeneration: p110α and p110δ. However, in the CNS, axonal PIP3 decreases with development at the time when axon transport declines and regenerative competence is lost. Overexpressing p110α in CNS neurons had no effect; however, expression of p110δ restored axonal PIP3 and increased regenerative axon transport. p110δ expression enhanced CNS regeneration in both rat and human neurons and in transgenic mice, functioning in the same way as the hyperactivating H1047R mutation of p110α. Furthermore, viral delivery of p110δ promoted robust regeneration after optic nerve injury. These findings establish a deficit of axonal PIP3 as a key reason for intrinsic regeneration failure and demonstrate that native p110δ facilitates axon regeneration by functioning in a hyperactive fashion.
- MeSH
- axony * MeSH
- centrální nervový systém MeSH
- dospělí MeSH
- fosfatidylinositol-3-kinasy * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- neurony MeSH
- regenerace nervu MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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