Authors: Bogdan Mircea PETRESCU, Sorin RIGA, Octavian VASILIU, Andrei Gabriel MANGALAGIU


Tau is a microtubule-associated protein, representing the main component of the intracellular filamentous inclusions involved in the pathogenesis of several neurodegenerative disorders, named tauopathies. This protein is supposed to be essential for the regulation of microtubule structure and dynamics in normal neurons but, when hyperphosphorylated, it aggregates in neurofibrillary tangles, as in the brain of Alzheimer Dementia (AD) patients. Current approved treatment for AD (donepezil, galantamine, rivastigmine and memantine) is only symptomatic and has, unfortunately, modest benefits. Although recent substantial progress has been made in the research of tau pathology, the mechanisms underlying tau-induced neurodegeneration remain not completely understood. Therapies targeting β-amyloid have been explored for more than two decades, but most of them have failed to show clinical benefits in phase III trials. Therefore, researchers are turning their attention to tau-targeting therapies, since tau protein appears to be better correlated with the severity of cognitive decline than β-amyloid. Currently, most anti-tau agents in clinical trials are immunotherapies occurring in an early stage of research. In the present study, we present the biochemical properties of tau protein, the pathogenesis underlying tau-induced neurodegenerative diseases, and ongoing tau-targeted strategies for therapeutic modulation.

  • Alzheimer dementia
  • glycogen-synthase kinase-3β
  • immunotherapy
  • N-methyl-D-aspartate
  • neurodegenerative diseases
  • protein phosphatase 2A
  • tau protein
  • tauopathies