Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies

Goran Šimić*, Mirjana Babić Leko, Selina Wray, Charles Harrington, Ivana Delalle, Nataša Jovanov-Milošević, Danira Bažadona, Luc Buée, Rohan de Silva, Giuseppe Di Giovanni, Claude Wischik, Patrick R. Hof

*Corresponding author for this work

Research output: Contribution to journalReview article

158 Citations (Scopus)
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Abstract

Abnormal deposition of misprocessed and aggregated proteins is a common final pathway of most neurodegenerative diseases, including Alzheimer’s disease (AD). AD is characterized by the extraneuronal deposition of the amyloid β (Aβ) protein in the form of plaques and the intraneuronal aggregation of the microtubule-associated protein tau in the form of filaments. Based on the biochemically diverse range of pathological tau proteins, a number of approaches have been proposed to develop new potential therapeutics. Here we discuss some of the most promising ones: inhibition of tau phosphorylation, proteolysis and aggregation, promotion of intra- and extracellular tau clearance, and stabilization of microtubules. We also emphasize the need to achieve a full understanding of the biological roles and post-translational modifications of normal tau, as well as the molecular events responsible for selective neuronal vulnerability to tau pathology and its propagation. It is concluded that answering key questions on the relationship between Aβ and tau pathology should lead to a better understanding of the nature of secondary tauopathies, especially AD, and open new therapeutic targets and strategies.

Original languageEnglish
Article number6
Number of pages27
JournalBiomolecules
Volume6
Issue number1
Early online date6 Jan 2016
DOIs
Publication statusPublished - Mar 2016

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Keywords

  • Alzheimer’s disease
  • Amyloid β
  • Microtubules
  • Neurofibrillary degeneration
  • Neuropathology
  • Phosphorylation
  • Protein aggregation
  • Protein oligomerization
  • Tau protein
  • Tauopathies

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry
  • Molecular Biology

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