Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/50999
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Campo DC | Valor | Idioma |
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dc.contributor.author | Li, Hai | por |
dc.contributor.author | Kuwajima,Takaaki | por |
dc.contributor.author | Oakley, Derek | por |
dc.contributor.author | Nikulina, Elena | por |
dc.contributor.author | Hou, Jianwei | por |
dc.contributor.author | Yang, Wan Seok | por |
dc.contributor.author | Lowry, Emily Rhodes | por |
dc.contributor.author | Lamas, Nuno Jorge | por |
dc.contributor.author | Amoroso, Mackenzie Weygandt | por |
dc.contributor.author | Croft, Gist F. | por |
dc.contributor.author | et. al. | por |
dc.date.accessioned | 2018-02-23T17:32:30Z | - |
dc.date.available | 2018-02-23T17:32:30Z | - |
dc.date.issued | 2016-07-13 | - |
dc.identifier.citation | Li, H., Kuwajima, T., Oakley, D., Nikulina, E., Hou, J., Yang, W. S., ... & Hosur, R. (2016). Protein prenylation constitutes an endogenous brake on axonal growth. Cell reports, 16(2), 545-558 | por |
dc.identifier.issn | 2211-1247 | - |
dc.identifier.uri | https://hdl.handle.net/1822/50999 | - |
dc.description.abstract | Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early-versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans. | por |
dc.description.sponsorship | Samaher Fageiry and Cyndel Vollmer for help with the culture model, Kevin Eggan and collaborators for kindly providing Hb9::GFP human ESC reporter lines, and Chuck Karan and members of the High-Throughput Screening and Chemistry Shared Facility for support and technical guidance. We thank the He lab (Harvard) for training in optic nerve crush. We are grateful to members of the Project A.L.S., Henderson, Wichterle, and Stockwell laboratories at Columbia University for much help and continuous critical discussion. We thank our Biogen colleagues Alex McCampbell, Sha Mi, and Richard Ransohoff for critical reading of the manuscript. This work received invaluable support from the New York State Spinal Cord Injury Research Board (NYS-SCIRB C020923), P2ALS, Target ALS, the Tow Foundation, the SMA Foundation, Project A.L.S., NYSTEM (C026715), The Helmsley Charitable Trust, NINDS R01-NS056422 and NS072428, and the Columbia MD-PhD program. Brent R. Stockwell is an Early Career Scientist of the Howard Hughes Medical Institute, and this research was additionally funded by the NIH (5R01CA097061 and R01CA161061, to B.S.) and New York State Stem Cell Science (C026715) | por |
dc.language.iso | eng | por |
dc.publisher | Elsevier 1 | por |
dc.rights | openAccess | por |
dc.title | Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth | por |
dc.type | article | por |
dc.peerreviewed | yes | por |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S2211124716307379 | por |
oaire.citationStartPage | 545 | por |
oaire.citationEndPage | 558 | por |
oaire.citationIssue | 2 | por |
oaire.citationVolume | 16 | por |
dc.date.updated | 2018-01-25T12:07:29Z | - |
dc.identifier.doi | 10.1016/j.celrep.2016.06.013 | por |
dc.identifier.pmid | 27373155 | por |
dc.subject.fos | Ciências Médicas::Medicina Básica | por |
dc.description.publicationversion | info:eu-repo/semantics/publishedVersion | por |
dc.subject.wos | Science & Technology | por |
sdum.journal | Cell Reports | por |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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li, lamas, 2016.pdf | 4,7 MB | Adobe PDF | Ver/Abrir |