HDAC6 mutations rescue human tau-induced microtubule defects in Drosophila

 

The search for cures and understanding of diseases is paramount to survival of the fittest. The use of the Drosophila (common fruit fly) is being used to account for neural transmissiion in Alzheimer Dissease. Amazingly the HDAC6 mutation is seen not only in this small organism but also in mice. One more step toward understanding and hopefully a cure or at least a delay in Alheimer patients.

Neurons from the brains of Alzheimer’s disease (AD) and related tauopathy patients contain neurofibrillary tangles composed of hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs); however, tau hyperphosphorylation leads to loss of this function with consequent MT destabilization and neuronal dysfunction. Accordingly, MT-stabilizing drugs such as paclitaxel and epothilone D have been shown as possible therapies for AD and related tauopathies. However, MT-stabilizing drugs have common side effects such as neuropathy and neutropenia. To find previously undescribed suppressors of tau-induced MT defects, we established a Drosophila model ectopically expressing human tau in muscle cells, which allow for clear visualization of the MT network. Overexpressed tau was hyperphosphorylated and resulted in decreased MT density and greater fragmentation, consistent with previous reports in AD patients and mouse models.

http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1207586110/-/DCSupplemental

Evolution of neuronal changes in the course of Alzheimer's disease. http://www.ncbi.nlm.nih.gov/pubmed/9700651

Single-Neuron Observations Mark Steps in Alzheimer's Disease

Apr. 20, 2012 http://www.sciencedaily.com/releases/2012/04/120420105831.htm