Recent studies have implicated components of the intracellular transport pathway as targets for the development of neuronal disease, indicating that this pathway can be crucial for the incidence of neuronal dysfunction. Our previous work implicated that defects in this pathway is an early event in two neurodegenerative diseases: Alzheimer's Disease (AD) and Huntington's/other polyQ diseases (HD/polyQ). In this proposal we will test how a novel therapeutic intervention can be directly targeted to this pathway using nanotechonology, fruit fly genetics, and high resolution live microscopy techniques. Our goal is to develop a functional "synthetic-vehicle" using a novel nanoparticle, which can carry a caged modifier drug directly to defects observed in this pathway. Once the drug arrives at the defective site, the drug will be released and the modifier affects of the drug will be evaluated. The rational for caging the drug inside the nanoparticle is to prevent deleterious side effects that the drug may have on the normal functions of an organism. To accomplish these goals we will build tagged nanoparticles for directed movement within a neuron. ORMOSIL is a novel nanoparticle that has many advantages over other particles. It is small in size, has a porous surface and in in vitro assays the uptake of these particles was significantly higher with no indication of toxicity. As we have recently discovered and published, these particles are biocompatible and are not toxic to whole organisms. These particles readily incorporate into neuronal cells and do not interfere with normal cellular process.