A walk through tau therapeutic strategies

Research output: Contribution to journalReview article

Abstract

Tau neuronal and glial pathologies drive the clinical presentation of Alzheimer's disease and related human tauopathies. There is a growing body of evidence indicating that pathological tau species can travel from cell to cell and spread the pathology through the brain. Throughout the last decade, physiological and pathological tau have become attractive targets for AD therapies. Several therapeutic approaches have been proposed, including the inhibition of protein kinases or protein-3-O-(N-acetyl-beta-D-glucosaminyl)-L-serine/threonine Nacetylglucosaminyl hydrolase, the inhibition of tau aggregation, active and passive immunotherapies, and tau silencing by antisense oligonucleotides. New tau therapeutics, across the board, have demonstrated the ability to prevent or reduce tau lesions and improve either cognitive or motor impairment in a variety of animal models developing neurofibrillary pathology. The most advanced strategy for the treatment of human tauopathies remains immunotherapy, which has already reached the clinical stage of drug development. Tau vaccines or humanised antibodies target a variety of tau species either in the intracellular or extracellular spaces. Some of them recognise the amino-terminus or carboxy-terminus, while others display binding abilities to the proline-rich area or microtubule binding domains. The main therapeutic foci in existing clinical trials are on Alzheimer's disease, progressive supranuclear palsy and non-fluent primary progressive aphasia. Tau therapy offers a new hope for the treatment of many fatal brain disorders. First efficacy data from clinical trials will be available by the end of this decade.

Details

Authors
  • Santosh Jadhav
  • Jesus Avila
  • Michael Schöll
  • Gabor G. Kovacs
  • Enikö Kövari
  • Rostislav Skrabana
  • Lewis D. Evans
  • Eva Kontsekova
  • Barbara Malawska
  • Rohan de Silva
  • Luc Buee
  • Norbert Zilka
Organisations
External organisations
  • CIBER Enfermedades Neurodegenerativas (CIBERNED)
  • University of Gothenburg
  • University College London
  • Geneva University Hospital
  • University of Cambridge
  • Jagellonian University
  • University of Lille Nord de France
  • Institute of Neuroimmunology, Slovak Academy of Sciences
  • Axon Neuroscience SE
  • Autonomous University of Madrid
  • Medical University of Vienna
  • Lille University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology

Keywords

  • Aggregation, Alzheimer’s disease, Immunotherapy, PET imaging, Tau vaccines, Tauopathies, Therapeutic interventions
Original languageEnglish
Number of pages1
JournalActa neuropathologica communications
Volume7
Issue number1
Publication statusPublished - 2019 Feb 15
Publication categoryResearch
Peer-reviewedYes