2. Academic Validation
  3. A small molecule accelerates neuronal differentiation in the adult rat

A small molecule accelerates neuronal differentiation in the adult rat

  • Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16542-7. doi: 10.1073/pnas.1010300107.
Heiko Wurdak 1,  Shoutian Zhu,  Kyung Hoon Min,  Lindsey Aimone,  Luke L Lairson,  James Watson,  Gregory Chopiuk,  James Demas,  Bradley Charette,  Rajkumar Halder,  Eranthie Weerapana,  Benjamin F Cravatt,  Hollis T Cline,  Eric C Peters,  Jay Zhang,  John R Walker,  Chunlei Wu,  Jonathan Chang,  Tove Tuntland,  Charles Y Cho,  Peter G Schultz
Affiliations

Affiliation

  • 1 The Skaggs Institute of Chemical Biology and Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
PMID: 20823227 DOI: 10.1073/pnas.1010300107
Abstract

Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.

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