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Tau-induced neurodegeneration: mechanisms and targets

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Abstract

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau’s functions in microtubule assembly and stabilization and with regard to its interactions with other proteins. We describe and analyze important post-translational modifications: hyperphosphorylation, ubiquitination, glycation, glycosylation, nitration, polyamination, proteolysis, acetylation, and methylation. We discuss how these post-translational modifications can alter tau’s biological function. We analyze the role of mitochondrial health in neurodegeneration. We propose that microtubules could be a therapeutic target and review different approaches. Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and propose a mechanism of neurodegeneration.

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Correspondence to Alejandra del C. Alonso.

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Beharry, C., Cohen, L.S., Di, J. et al. Tau-induced neurodegeneration: mechanisms and targets. Neurosci. Bull. 30, 346–358 (2014). https://doi.org/10.1007/s12264-013-1414-z

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