Tau tangles and Ab plaques are the two hallmark pathological lesions in AD and are known to be regulated Pro-directed phosphorylation of tau and APP, but nothing was known whether they are further regulated. Our lab is the first to show that Pin1 is inhibited in human AD neurons by multiple age-related mechanisms, leading to the accumulation of pT231-tau and pT668-APP in the potential pathogenic cis conformation, providing a molecular link between tangles and plaques (Nature 1999, 2003, 2006). Our unexpected discovery that Pin1 has the opposite impact on cancer and AD has been confirmed by including epidemiological studies and accepted as #6 of the NCI’s inaugural Provocative Questions (CA-11-012).
Dr. Lu Laboratory and Dr. Zhou Laboratory, Western University, 1400 Western Road, SDRI Room 107, London, Ontario N6G 2V4, Canada. The co-crystal structures of Pin1 and its inhibitors are generated by Shaunik Sharma using Pymol.
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