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A walk through tau therapeutic strategies.

Review article
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
Published in Acta neuropathologica communications
Volume 7
Issue 1
ISSN 2051-5960
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Wallenberg Centre for Molecular and Translational Medicine
Language en
Links dx.doi.org/10.1186/s40478-019-0664-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Neurosciences

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.

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