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          Institute: MPI für Neurobiologie     Collection: Axonal Growth and Regeneration     Display Documents

ID: 475561.0, MPI für Neurobiologie / Axonal Growth and Regeneration
A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration
Authors:Usher, L. C.; Johnstone, A.; Ertürk, A.; Hu, Y.; Strikis, D.; Wanner, I. B.; Moorman, S.; Lee, W. L.; Min, J.; Ha, H. H.; Duan, Y. L.; Hoffman, S.; Goldberg, J. L.; Bradke, F.; Chang, Y. T.; Lemmon, V. P.; Bixby, J. L.
Date of Publication (YYYY-MM-DD):2010-03-31
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Issue / Number:13
Start Page:4693
End Page:4706
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:A major barrier to regeneration of CNS axons is the presence of growth-inhibitory proteins associated with myelin and the glial scar. To identify chemical compounds with the ability to overcome the inhibition of regeneration, we screened a novel triazine library, based on the ability of compounds to increase neurite outgrowth from cerebellar neurons on inhibitory myelin substrates. The screen produced four "hit compounds," which act with nanomolar potency on several different neuronal types and on several distinct substrates relevant to glial inhibition. Moreover, the compounds selectively overcome inhibition rather than promote growth in general. The compounds do not affect neuronal cAMP levels, PKC activity, or EGFR (epidermal growth factor receptor) activation. Interestingly, one of the compounds alters microtubule dynamics and increases microtubule density in both fibroblasts and neurons. This same compound promotes regeneration of dorsal column axons after acute lesions and potentiates regeneration of optic nerve axons after nerve crush in vivo. These compounds should provide insight into the mechanisms through which glial-derived inhibitors of regeneration act, and could lead to the development of novel therapies for CNS injury.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Axonal Growth and Regeneration (Bradke)
External Affiliations:[Usher, Lynn C.; Johnstone, Andrea; Strikis, Dinara; Wanner, Ina B.; Lemmon, Vance P.; Bixby, John L.] Univ Miami, Miller Sch Med, Miami Project Cure Paralysis, Miami, FL 33136 USA.; [Bixby, John L.] Univ Miami, Miller Sch Med, Dept Pharmacol, Miami, FL 33136 USA.; [Lemmon, Vance P.; Bixby, John L.] Univ Miami, Miller Sch Med, Dept Neurol Surg, Miami, FL 33136 USA.; [Hu, Ying; Duan, Yuanli; Goldberg, Jeffrey L.] Univ Miami, Miller Sch Med, Dept Ophthalmol, Miami, FL 33136 USA.; [Johnstone, Andrea; Wanner, Ina B.; Goldberg, Jeffrey L.; Lemmon, Vance P.; Bixby, John L.] Univ Miami, Miller Sch Med, Neurosci Program, Miami, FL 33136 USA.; [Hoffman, Stanley] Med Univ S Carolina, Dept Rheumatol, Charleston, SC 29425 USA.; [Lee, Wook; Min, Jaeki; Ha, Hyung-Ho; Chang, Young-Tae] Natl Univ Singapore, Dept Chem, Singapore 117543, Singapore.; [Moorman, Sanne] Univ Utrecht, Program Neurosci & Cognit, NL-3584 CH Utrecht, Netherlands.
Identifiers:ISI:000276178000020 [ID No:1]
ISSN:0270-6474 [ID No:2]
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