Scientists identify breakthrough molecules

April 20, 2010, 1:00 a.m.

Stanford scientists have identified multiple synthetic molecules that mimic a key protein in the brain involved in learning and memory. The protein, called BDNF, becomes inactive in degenerative diseases like Huntington’s and Alzheimer’s and declines naturally with age.

The new molecules show promise for creating drug therapies for these and other neurodegenerative diseases.

Frank Longo of the Stanford School of Medicine published the findings Monday in the Journal of Clinical Investigation; other authors included Tao Yang of Stanford and Steve Massa of UC-San Francisco and the San Francisco Veterans Affairs Medical Center.

Massa created a computer database through which to identify the compounds. The database identified substances similar chemically to BDNF, and from those 200 molecules, 17 were selected based on toxicity, solubility and other specifications.

Yang then did most of the bioassays of the identified chemicals at Stanford. He tested whether or not the molecules could keep neurons in a dish from dying, like BDNF.

BDNF promotes neuron growth and synapse formation within the brain. The complex protein supports existing neurons and helps them make new connections. In areas where new neurons do grow in the brain, BDNF helps facilitate that process.

However, BDNF cannot be used directly as a therapy in the brain for diseases where it is less active because it does not survive for long in blood and cannot cross the blood-brain barrier. These molecules are a breakthrough since they can replicate BDNF’s effects while overcoming its chemical problems as a treatment, making them potentially good candidates for future drug studies.

— Julia Brownell

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