TY - JOUR T1 - A Chemical Screen Identifies Novel Compounds That Overcome Glial-Mediated Inhibition of Neuronal Regeneration JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4693 LP - 4706 DO - 10.1523/JNEUROSCI.0302-10.2010 VL - 30 IS - 13 AU - Lynn C. Usher AU - Andrea Johnstone AU - Ali Ertürk AU - Ying Hu AU - Dinara Strikis AU - Ina B. Wanner AU - Sanne Moorman AU - Jae-Wook Lee AU - Jaeki Min AU - Hyung-Ho Ha AU - Yuanli Duan AU - Stanley Hoffman AU - Jeffrey L. Goldberg AU - Frank Bradke AU - Young-Tae Chang AU - Vance P. Lemmon AU - John L. Bixby Y1 - 2010/03/31 UR - http://www.jneurosci.org/content/30/13/4693.abstract N2 - 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. ER -