Brain-Derived Neurotrophic Factor (BDNF) plays a well-characterized role in synaptic plasticity, neuronal survival, neurogenesis, and resilience to depression and other neuropsychiatric disorders.
Most importantly, BDNF provides trophic support for existing neurons while encouraging the reorganization, growth and regeneration of new neurons and synapses.
BDNF is an endogenous neuropeptide that activates the TrkB receptor, and is biologically active in the hippocampus, cortex, and basal forebrain-areas essential to higher-order cognition. BDNF may also modulate the activity of neurotransmitters, including the alpha-7 nicotinic acetylcholine receptor.
The val66met is a relatively common polymorphism affecting the BDNF protein that is linked to the development of mood disorders.
Because of the importance of BDNF in regulating neuroplasticity into adulthood, BDNF has been suggested to play an essential role in the development of neurodegenerative disease. Numerous lines of evidence indicate that BDNF gene expression and its high-affinity receptor (Trk B) are reduced in post-mortem brain region from patients suffering from neurodegenerative disease.
The Challenges of Delivery To The CNS
As decreased circulating BDNF has been observed in Alzheimer’s disease (AD), one might imagine that exogenously delivering BDNF into the brain might be a valuable therapeutic strategy. However, BDNF does not readily cross the blood brain barrier (BBB), may result in Trk B receptor down regulation, and increases neuronal excitability. Therefore, crudely pumping BDNF into the CNS could hypothetically result in seizures.
When administered intraventricularly or intrathecally, BDNF infusion results in little BBB penetration, which may explain why clinical trials using this approach have been disappointing.
Biomedical scientists have turned to other more indirect strategies to enhance BDNF signaling. However, clinical trials are also viral vector based strategies to insert a promoter upstream of the BDNF gene that would dramatically enhance gene expression. One such pharmaceutical company pursuing this approach is Sangamo Biosciences.
Classes of drugs, nutraceuticals and lifestyle factors that Increase BDNF or Indirectly Enhance BDNF signaling include the following:
AMPA Receptor Modulators
Peptide BDNF Mimetics
Nutraceuticals (Gingko biloba, zinc, D-serine and others)
Exercise and Dietary Flavonoids and Anthocyanins (especially blueberries and cacao flavonoids)
Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011;10(3):209-19.
Fumagalli F, Racagni G, Riva MA. The expanding role of BDNF: a therapeutic target for Alzheimer’s disease?. Pharmacogenomics J. 2006;6(1):8-15.