Tau-induced neurodegeneration: mechanisms and targets

Neurosci Bull. 2014 Apr;30(2):346-58. doi: 10.1007/s12264-013-1414-z. Epub 2014 Apr 15.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dementia / metabolism*
  • Dementia / pathology
  • Humans
  • Microtubules / metabolism
  • Microtubules / pathology
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Protein Processing, Post-Translational / physiology*
  • tau Proteins / metabolism*


  • tau Proteins