| Research Abstract |
Neurofibrillary tangles (NFT) is one of the major pathological changes in brain of Alzheimer's disease patients. NFT is composed of the hyperphosphorylated tau observed in tauopathy. Recently tau mutation has been found in familial case of tauopathy, FTDP-17, which is characterized by NFT and loss of neurons. This finding suggests that the mutant tau protein causes NFT and neuronal death. Moreover, NFT-like pathological changes are present in cortex, hippicampus or spinal cord of transgenic mice expressing the mutant tau protein. These mice have shown behavioral disorders. Hence tau may be involved in developing the neurodegeneration of Alzheimer's disease and other tauopathies. However, a role of tau in neurodegeneration remains unclear. To understand the mechanism of neurodegeneration through tau, we screen proteins associating with tau protein by yeast two-hybrid system. Yeast (CG1945-T4R) expressing GAL4-DNA-BD/tau fusion proitein was transformed by human brain cDNA library constructed with pACT2, GAL4AD expression vector. Two positive clones associating with tau were selected on minimal SD plate without Trp, Leu and His. Interaction between tau and the expressed proteins of positive clones in culture cells were confirmed by immunoprecipitaion and immunostaining.
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