RT Journal Article SR Electronic T1 A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4693 OP 4706 DO 10.1523/JNEUROSCI.0302-10.2010 VO 30 IS 13 A1 Lynn C. Usher A1 Andrea Johnstone A1 Ali Ertürk A1 Ying Hu A1 Dinara Strikis A1 Ina B. Wanner A1 Sanne Moorman A1 Jae-Wook Lee A1 Jaeki Min A1 Hyung-Ho Ha A1 Yuanli Duan A1 Stanley Hoffman A1 Jeffrey L. Goldberg A1 Frank Bradke A1 Young-Tae Chang A1 Vance P. Lemmon A1 John L. Bixby YR 2010 UL http://www.jneurosci.org/content/30/13/4693.abstract AB 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.