Cited by 93Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Tau-directed drug discovery for alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors

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Brunden, Kurt R., Ballatore, Carlo, Crowe, Alex, Smith,, Amos B., Lee, Virginia M.-Y., Trojanowski, John Q.·2010·Experimental Neurology

Abstract

The microtubule-associated protein tau forms insoluble filaments that deposit as neurofibrillary tangles (NFTs) in the brains of those with Alzheimer's disease (AD) and other related neurodegenerative disorders. The presence of both NFTs and amyloid beta (Abeta)-containing senile plaques within the brain is required to confirm the diagnosis of AD. However, the demonstration that familial AD can be caused by mutations that result in increased Abeta production has resulted in AD drug discovery strategies that are largely focused on reducing brain Abeta levels, with substantially less emphasis on tau-directed approaches. This trend may be changing, as there are an increasing number of research programs that are exploring ways to reduce NFTs in AD and related tauopathies. We briefly review recent advances in tau-based drug discovery, with an emphasis on the identification of compounds that inhibit the assembly of tau into multimers and fibrils.

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Crossref · 10.1016/j.expneurol.2009.08.031

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  • Current investigative tau-directed therapeutics have focused on aggregation inhibitors, activators of protein clearance through autophagy, and inhibition of tau kinases.

    “Current investigative tau-directed therapeutics have focused on aggregation inhibitors (Brunden et al., 2010; Panza et al., 2016; Bulic et al., 2009), activators of protein clearance through autophagy (Boland et al., 2008; Krüger et al., 2012; Medina, 2018; Wang and Mandelkow, 2012; Rubinsztein et al., 2015), and inhibition of tau kinases (Dolan and Johnson, 2010; Medina, 2018).”

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Research works printed but not linked: 3

  1. [4]Avila J Tau and tauopathies: tau phosphorylation and tau assembly Febs Journal 2006a 273 23
  2. [18]Cleveland DW Connolly JA Kalnins VI Spiegelman BM Kirschner MW Physical-Properties and Cellular Localization of Tau, A Microtubule Associated Protein Which Induces Assembly of Purified Tubulin Journal of Cell Biology 1977a 75 A283
  3. [43]Hong M Zhukareva V Vogelsberg-Ragaglia V Wszolek Z Reed L Miller BI Geschwind DH Bird TD McKeel D Goate A Morris JC Wilhelmsen KC Schellenberg GD Trojanowski JQ Lee VMY Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17 Science 1998a 282 1914 1917 9836646

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Authors
Brunden, K. R., Ballatore, C., Crowe, A., Smith, Lee, V. M.-Y., & Trojanowski, J. Q.
Affiliations
University of Pennsylvania (US)
Corresponding author
Brunden, Kurt R.
Venue
Experimental Neurology
Publisher
Elsevier BV
Published
2010-06
Volume
223
Issue
2
Pages
304-310
ISSN
0014-4886 (ISSN-L)
OpenAlex
W1969483518
Cited by
93
References
78
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 9 · 2014: 9 · 2013: 5 · 2012: 10
FWCI
0.91
Type
journal article
Language
en
Open access
Locations
  • Experimental Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (P01 AG09215, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG17586, P01 NS-044233, P30 AG10124, PO1 AG19724, UO1 AG24904)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
tau protein, Alzheimer's disease, tauopathy, neurofibrillary tangles, tau fibrils, drug discovery, amyloid-beta, amyloid plaques, familial Alzheimer's disease
MeSH terms
Alzheimer Disease, Humans, Neurofibrillary Tangles, tau Proteins, Tauopathies, Drug Discovery

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