Details

Autor(en) / Beteiligte

• Tuszynski, Mark H
• Nagahara, Alan H

Titel

Potential therapeutic uses of BDNF in neurological and psychiatric disorders

Ist Teil von

• Nature reviews. Drug discovery, 2011-03, Vol.10 (3), p.209-219

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Brain-derived neurotrophic factor (BDNF), which acts through its receptor tropomyosin-related kinase receptor type B, has diverse effects on neuronal function and survival in the adult brain. Nagahara and Tuszynski review the potential therapeutic use of BDNF in the treatment of various disorders of the central nervous system, such as Alzheimer's disease, and discuss the challenges to effective delivery of BDNF and possible strategies to overcome them. 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.