Dementia, loss of intellectual abilities that is severe enough to interfere with social or occupational functioning, is a major socioeconomic problem. Two of the most common causes of dementia are Alzheimer's disease (AD), comprising 50-70% of all cases, and Fronto Temporal Dementia (FTD), which makes up to 50% of dementias before age 60. Though there have been major efforts to therapeutically treat these diseases, these dementias at present are not curable. AD brain is characterized by the presence of distinct lesions caused by formation of filamentous deposits of abnormal brain proteins in neurons. These filamentous deposits are caused by tau, a prominent intra-cellular accumulation of microtubule (MT) associated protein. Several studies have shown that tau protein negatively regulate kinesin, a molecular motor that mediate transport of proteins, RNAs and organelles such as mitochondria to synapses. Furthermore, reduction in tau improves memory loss in mice. Thus, positive regulator of kinesin will have therapeutic value. My previous finding suggest that modulating kinesin function enhances synaptic activity. Most importantly, kinesin activity is physiologically upregulated during memory storage. This proposal aims to identify and characterize small molecules that enhance molecular transport mediated by kinesin motor protein in mammalian neurons. We have developed a high throughput-screening (HTS) assay with the help of funding from ADDF. Now we propose to use this assay to screen a large library of compounds to identify compounds that are enhancers and inhibitors of kinesin motility in neurons. We will validate these results in cell-based assays and also in intact animal by mouse behavioral assays.