A small molecule accelerates neuronal differentiation in the adult rat

• DOI: 10.1073/pnas.1010300107
• Publication Date: 2010-09-08T02:21:32Z
• Authors: Heiko Wurdak; 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
• Keywords: Neural Development

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