10.1523/JNEUROSCl.0302-10.2010Journal of Neuroscience30134693-4706JNRS

Bixby, J.L.

Bradke, F.

Chang, Y.-T.

Duan, Y.

Ertürk, A.

Goldberg, J.L.

Ha, H.-H.

Hoffman, S.

Hu, Y.

Johnstone, A.

Lee, J.-W.

Lemmon, V.P.

Min, J.

Moorman, S.

Strikis, D.

Usher, L.C.

Wanner, I.B.

PubMed

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

Usher, Lynn C

Johnstone, Andrea

Ertürk, Ali

Hu, Ying

Strikis, Dinara

Wanner, Ina B

Moorman, Sanne

Lee, Jae-Wook

Min, Jaeki

Ha, Hyung-Ho

Duan, Yuanli

Hoffman, Stanley

Goldberg, Jeffrey L

Bradke, Frank

Chang, Young-Tae

Lemmon, Vance P

Bixby, John L

University of Miami: Scholarship Miami

Journal of Neuroscience

A chemical screen identifies novel compounds that overcome glial-mediated inhibition of neuronal regeneration

ScholarBank@NUS

Usher, L.

Wanner, I.

Lee, W.

Ha, H.

Goldberg, J.

Chang, Y.

Lemmon, V.

Bixby, J.

MPG.PuRe

A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration

Usher, L. C.

Wanner, I. B.

Lee, W. L.

Ha, H. H.

Duan, Y. L.

Goldberg, J. L.

Chang, Y. T.

Lemmon, V. P.

Bixby, J. L.

Max Planck Society eDoc Server

http://dx.doi.org/10.1523/JNEUROSCI.0302-10.2010

A chemical screen identifies novel compounds that overcome glial-mediated inhibition of neuronal regeneration

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University of Miami: Scholarship Miami

ScholarBank@NUS

MPG.PuRe

MPG.PuRe

Max Planck Society eDoc Server