Drug Discovery Opinion

Roles have been suggested for brain-derived neurotrophic factor (BDNF) – which helps to support neurons and also stimulates and controls neurogenesis – in preventing or treating degenerative diseases such amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease. The use of BDNF itself in therapy is limited by a poor pharmokinetic profile including rapid metabolism and poor CNS penetration. BDNF elicits at least some of its effects through binding to the high affinity tyrosine kinase receptor B, TrkB, and investigators at Emory University School of Medicine have now identified a small, high-affinity molecule that can also activate signalling through TrkB.

7,8-Dihydroxyflavone was shown to protect wild-type, but not TrkB-deficient, neurons from apoptosis. Following intraperitoneal administration, the compound was also found to activate TrkB in the brain and to be protective in animal models of seizure, stroke and Parkinson’s disease. The compound was also found to have low toxicity on chronic dosing. Although favonoids such as 7,8-dihydroxyflavone occur in a wide range of foodstuffs, levels obtained from a normal diet are believed to be insufficient for a sustained effect.

The study is published in the online early edition of PNAS.

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