What role does BDNF play in the HD disease cascade?
The central nervous system (CNS) has a greater ability to recover from insult or injury than scientists had previously thought. For decades, the prevailing view was that the brain stopped developing after the first few years of life. Connections between the brain’s nerve cells could only be formed during a critical period early in life. After this critical period, it was thought that the brain was unable to form new connections. Thus, if a particular area of the adult brain was damaged or injured, nerve cells would not be able to regenerate, and the functions controlled by that area would be lost forever. However, new research suggests that this view is not entirely correct. Researchers now recognize that the brain continues to reorganize itself by forming new neural connections throughout life. This phenomenon, called neuroplasticity, allows nerve cells in the brain to compensate for injury and new situations or changes in the environment. (For more information on neuroplasticity, click here.)
In HD, it is thought that a mutant huntingtin protein gains a new function that is harmful to striatal nerve cells in the brain. (For more information on huntingtin protein, click here.) According to the recent discovery of neuroplasticity, these nerve cells should be able to compensate for such insults by simply generating new neural connections. However, it has been shown that once the striatal nerve cells die in people with HD, they do not re-form. Why is this the case? It turns out that mutant huntingtin protein decreases transcription of BDNF. Decreased transcription means that less BDNF is made by people who have HD. Nerve cells require BDNF not only to survive, but also to regenerate. By lowering levels of BDNF in the brain, mutant huntingtin acts as a devastating double-edged sword. First, nerve cells die because there isn’t enough BDNF to effectively combat neurodegeneration. Second, nerve cells are not able to regenerate because there still isn’t enough BDNF. It therefore appears that BDNF plays a crucial role in the degenerative process of HD.
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Last Modified: 12-28-05
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