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Potential therapeutic uses of BDNF in neurological and psychiatric disorders

Nature Reviews Drug Discovery volume 10, pages 209–219 (2011)Cite this article

Subjects

Key Points

  • Brain-derived neurotrophic factor (BDNF) is widely produced in the cortex throughout life, where it influences neuronal function. Levels of BDNF become deficient in the cerebral cortex in Alzheimer's disease.

  • In animal models of Alzheimer's disease, BDNF exhibits potent therapeutic effects that include prevention of cell death, stimulation of neuronal function, improvement in synaptic markers and improvements in learning and memory. Accordingly, BDNF represents a potentially promising therapeutic avenue in Alzheimer's disease.

  • Other neurological and psychiatric disorders — for example, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and depression — could also respond to BDNF treatment.

  • Therapeutic BDNF delivery to the brain is a major challenge. BDNF does not readily cross the blood–brain barrier, and widespread central administration causes intolerable adverse effects. Localized and sustained delivery of the growth factor will be required to treat many neurological disorders.

  • Gene therapy may be a useful method of delivering BDNF to specific brain regions in neurological disorders. For example, clinical trials involving BDNF gene delivery to the entorhinal and/or the hippocampal circuitry regions in Alzheimer's disease are planned.

  • Other methods for increasing BDNF levels in the brain include the use of small peptide mimetics, drug-induced increases in BDNF and even exercise. It remains to be established, however, whether these methods can induce sufficient increases in BDNF levels to effectively treat neurological diseases.

Abstract

The growth factor brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TRKB) are actively produced and trafficked in multiple regions in the adult brain, where they influence neuronal activity, function and survival throughout life. The diverse presence and activity of BDNF suggests a potential role for this molecule in the pathogenesis and treatment of both neurological and psychiatric disorders. This article reviews the current understanding and future directions in BDNF-related research in the central nervous system, with an emphasis on the possible therapeutic application of BDNF in modifying fundamental processes underlying neural disease.

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Figure 1: Summary of potential sites in the human brain for BDNF treatment for specific types of diseases.

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Acknowledgements

This work is supported by the National Institutes of Health grant AG10435, the Veterans Administration, the Alzheimer's Association, the Shiley Family Foundation, and the Dr Miriam and Sheldon G. Adelson Medical Research Foundation.

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  1. Department of Neurosciences 0626, Center for Neural Repair, University of California, San Diego, La Jolla, 92093, California, USA

    Alan H. Nagahara & Mark H. Tuszynski

  2. Veterans Affairs Medical Center, San Diego, 92161, California, USA

    Mark H. Tuszynski

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Correspondence to Mark H. Tuszynski.

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Nagahara, A., Tuszynski, M. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 10, 209–219 (2011). https://doi.org/10.1038/nrd3366

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