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A walk through tau therapeutic strategies

Jadhav, Santosh ; Avila, Jesus ; Schöll, Michael LU ; Kovacs, Gabor G. ; Kövari, Enikö ; Skrabana, Rostislav ; Evans, Lewis D. ; Kontsekova, Eva ; Malawska, Barbara and de Silva, Rohan , et al. (2019) In Acta neuropathologica communications 7(1).
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... (More)

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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publication status
published
subject
keywords
Aggregation, Alzheimer’s disease, Immunotherapy, PET imaging, Tau vaccines, Tauopathies, Therapeutic interventions
in
Acta neuropathologica communications
volume
7
issue
1
pages
1 pages
publisher
BioMed Central
external identifiers
  • scopus:85061577740
  • pmid:30767766
ISSN
2051-5960
DOI
10.1186/s40478-019-0664-z
language
English
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yes
id
45e1a2ca-249b-4284-929d-2206dc0799eb
date added to LUP
2019-02-25 12:32:56
date last changed
2020-04-02 02:21:48
@article{45e1a2ca-249b-4284-929d-2206dc0799eb,
  abstract     = {<p>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.</p>},
  author       = {Jadhav, Santosh and Avila, Jesus and Schöll, Michael and Kovacs, Gabor G. and Kövari, Enikö and Skrabana, Rostislav and Evans, Lewis D. and Kontsekova, Eva and Malawska, Barbara and de Silva, Rohan and Buee, Luc and Zilka, Norbert},
  issn         = {2051-5960},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Acta neuropathologica communications},
  title        = {A walk through tau therapeutic strategies},
  url          = {http://dx.doi.org/10.1186/s40478-019-0664-z},
  doi          = {10.1186/s40478-019-0664-z},
  volume       = {7},
  year         = {2019},
}