Affiliations: [a] Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei, Taiwan | [b] Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei, Taiwan | [c] Graduate Institute of Biochemical Science, College of Life Science, National Taiwan University, Taipei, Taiwan | [d] Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan | [e] Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
Correspondence:
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Correspondence to: Po-An Yeh, Institute of Biomedical Sciences, Academia Sinica, 128 Sec. 2 Academia Road, Nankang, Taipei 11529, Taiwan. Tel.: +886 2 2652 3532; Fax: +886 2 2782 7654; E-mail: paulanny@ntnu.edu.tw.
Abstract: The microtubule-associated tau protein has long been considered an axon-specific protein. Although many articles describe the subcellular localization of tau as regulated by post-modification in cultured cells, the intracellular regulation of its distribution in living animals has yet to be elucidated. In the present study, we demonstrate that phosphorylation alters tau polarity in Drosophila melanogaster. Interestingly, it was observed that expression of phosphorylation-incompetent tau impaired neurite growth more severely than either hyperphosphorylated or pseudophosphorylated tau. We also found that inducible expression of hyper- or pseudo-phosphorylated tau in adult flies strikingly prolonged their lifespan. This study offers an alternative tauopathic model by demonstrating that hyperphosphorylated tau has a beneficial effect on the nervous system. This is also corroborated by common effects seen in a variety of organisms in response to various stresses. We hope that this important animal model leads to a paradigm shift in thinking about hyperphosphorylated tau, which plays a protective role in nervous systems rather than the toxic role that many have historically been given to it.
Keywords: Alzheimer's disease, animal model, Drosophila, lifespan, neuroprotection, PP2A, protein localization, tau phosphorylation, tubulin polymerization
