Novel Microtubule-Based Hypothesis for Frontotemporal Dementia Leading to Therapy for Military Personnel and Veterans
Abstract
Frontotemporal degeneration is a condition suffered by many people wherein the nerves in the front part of the brain start to break down. This compromises the ability of these people to have normal cognitive functions, for example, manifesting as disinhibition of socially unacceptable behaviors. Frontotemporal degeneration can be caused by many things, but one of the chief causes is problems with a protein called tau. Tau is a protein that binds to little filaments in nerves called microtubules. Microtubules are like streets that allow nutrients and other substances to be carried in both directions along separate lanes. When there are problems with tau, traffic jams occur in the nerve in which substances that should be moving stop moving and pile up. Doctors generally think this is because the number of microtubules drops in the axon, and the end result is the breakdown of the nerve because the right substances cannot be delivered to where they need to be. Unfortunately, there are no medicines that can treat such diseases. This might be because doctors have this wrong. Maybe the real reason for the traffic jams is not fewer streets, but a mix up in the directionality of the lanes. Imagine if cars started switching into the wrong lanes moving in the opposite direction. Traffic jams and pileups would be inevitable. As important as this is to get figured out, the effort to do so is actually not so difficult, with good progress entirely achievable in 2 years. In this grant application, the scientists proposing the work will use human neurons in culture that were developed from stem cells with abnormal tau like that of patients suffering from this kind of disease. They will test whether the microtubules are switched around in their directionality from how they should be. Then, the scientists will test whether medicines that switch them back to normal can correct the traffic jams and restore the nerves to better health. If this works, the 2-year study will open the door to helping people suffering from frontotemporal degeneration due to tau problems and possibly even other forms of the disease that are caused by problems with other proteins. Frontotemporal degeneration is a disease suffered in the general population, but is exacerbated in Soldier and Veteran populations, for example, because blast injuries to the brain increase the chances of getting it. Thus, the proposed studies fit well with the priorities of the US Department of Defense.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110189
Entities
People
- Peter W Baas
Organizations
- Drexel University
- United States Army