The discovery of the relation between huntingtin and BDNF is a major step in the path to finding a treatment for HD. Previously, it was thought that mutant huntingtin gained a new function that caused neurodegeneration in the brain. However, researchers now know that HD is caused, not only by this toxic gain of function of mutant huntingtin, but also by a loss of function of normal huntingtin. Normal huntingtin is necessary because its presence allows for the production of BDNF. In the absence of normal huntingtin, BDNF production drops drastically. This realization is a major step because it indicates that treatments need to be aimed not only at preventing mutant huntingtin toxicity, but also at restoring normal huntingtin function.
A simple way to restore the loss of normal huntingtin function in the case of decreased BDNF production would be to administer BDNF into nerve cells. Indeed, numerous laboratories are currently trying to develop viable ways to carry out this kind of procedure. However, there are still several steps that need to be taken before a drug can be developed based on this research. Scientists need to understand exactly how huntingtin "communicates” to the BDNF gene to increase its activity. Trials are already under development to deliver BDNF via gene therapy to HD transgenic mice and researchers are confident that research in this area will progress rapidly.
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-D. McGee, 1-1-06
For further reading:
Connor, J. et al. (1997). Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport. Society for Neuroscience 17(7): 2295-2313. This article is fairly complex. It describes the likely method through which BDNF exerts its effects within the brain.
Gomez-Pinilla, F., Ying, Z., Roy, R., Molteni, R., & V. Edgerton. (2002). Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol. 88(5): 2187-95.
This article is easy to understand and it describes the effect of exercise on brain health and plasticity.
Vaynman, S., Ying, Z., & F. Gomez-Pinilla. (2003). Interplay between brain-derived neurotrophic factor and signal transduction modulators in the regulation of the effects of exercise on synaptic-plasticity. Neuroscience 122(3): 647-57.
This article is fairly easy to read and it discusses the possible mechanisms through which exercise may influence levels of BDNF.
Zuccato C. et al. (2001) Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease.Science, 293, 493-496.
This is a technical article that describes how the beneficial activity of huntingtin is lost in people with HD and how this leads to decreased production of BDNF.
Zuccato C., Tartari T., Crotti C., Goffredo D., Valenza M., Conti L., Cataudella T., Leavitt B. R., Hayden M. R.,Timmusk T., Rigamonti D. & Cattaneo E. (2003) Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nature Genetics 35: 76-83.
This article is very technical. It describes in detail how normal huntingtin increases transcription of BDNF by silencing NSRE.
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Last Modified: 12-28-05
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