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. 2014 Apr 15;30(2):346–358. doi: 10.1007/s12264-013-1414-z

Tau-induced neurodegeneration: mechanisms and targets

Cindy Beharry 1, Leah S Cohen 1, Jing Di 1, Kawsar Ibrahim 1, Susan Briffa-Mirabella 1, Alejandra del C Alonso 1,✉
PMCID: PMC5562659  PMID: 24733656

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.

Keywords: tau, phosphorylation, neurodegeneration, tauopathies, mitochondria, microtubules, tubulin, kinases, phosphatases, Alzheimer’s disease

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