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A good mimic promotes nerve cell survival

Altered expression and/or function of the protein BDNF, which promotes nerve cell survival, generation, and function, have been implicated in several neurodegenerative conditions, including Alzheimer disease. Although several properties of BDNF preclude its therapeutic application, it has been suggested that molecules that stimulate the protein to which BDNF binds, TrkB, might have therapeutic potential. Now, a team of researchers, led by Frank Longo, at Stanford University School of Medicine, has developed a two-step screening strategy to identify small molecules that bind to TrkB but not other related proteins and, importantly, demonstrated that one of the compounds they identified prevented nerve cell degradation as efficiently as did BDNF in in vitro models of neurodegenerative conditions. Further, it improved motor learning after traumatic brain injury in rats, leading the authors to suggest that both their two-step approach to drug discovery and the compounds it yielded could prove useful in developing new therapeutics for the treatment of neurodegenerative conditions.

TITLE: Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents

AUTHOR CONTACT:
Frank M. Longo
Stanford University School of Medicine, Stanford, California, USA.
Phone: 650.724.3172; Fax: 650.498.4579; E-mail: longo@stanford.edu.

View this article at: http://www.jci.org/articles/view/41356?key=8bab18be763a793f72cd

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