Is presynaptic dysfunction in Huntington’s disease due to BDNF hypofunction?

Brain cells communciate by releasing chemicals called neurotransmitters. Neurotransmitter release is sustained during high activity by the process of activity-dependent bulk endocytosis (ADBE). A number of neurodegenerative conditions may be precipitated by dysfunctional neurotransmitter release, including Huntington’s Disease (HD). HD is associated with a defect in a molecule called brain-derived neurotrophic factor (BDNF). Interestingly, BDNF also inhibits ADBE, and we have discovered that ADBE is increased in HD neurons. Therefore we will test whether faulty BDNF is reponsible for increased ADBE in HD, which would reveal a new target for future therapy.