Cited by 286Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

Development of tau aggregation inhibitors for alzheimer's disease

Bulic, Bruno, Pickhardt, Marcus, Schmidt, Boris, Mandelkow, Eva‐Maria, Waldmann, Herbert, Mandelkow, Eckhard·2009·Angewandte Chemie International Edition

Abstract

Abstract Small molecules against Alzheimer's : The pathological aggregation of the tau protein is a major hallmark of neurodegenerative diseases such as Alzheimer's disease. The inhibition or reversal of tau aggregation is a potential therapeutic strategy that is currently undergoing clinical trials. The image shows pathological fibers assembled from tau protein, which are the main components of the neurofibrillary tangles of Alzheimer's disease. magnified image A variety of human diseases are suspected to be directly linked to protein misfolding. Highly organized protein aggregates, called amyloid fibrils, and aggregation intermediates are observed; these are considered to be mediators of cellular toxicity and thus attract a great deal of attention from investigators. Neurodegenerative pathologies such as Alzheimer's disease account for a major part of these protein misfolding diseases. The last decade has witnessed a renaissance of interest in inhibitors of tau aggregation as potential disease‐modifying drugs for Alzheimer's disease and other “tauopathies”. The recent report of a phase II clinical trial with the tau aggregation inhibitor MTC could hold promise for the validation of the concept. This Review summarizes the available data concerning small‐molecule inhibitors of tau aggregation from a medicinal chemistry point of view.

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Crossref · 10.1002/anie.200802621

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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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Authors
Bulic, B., Pickhardt, M., Schmidt, B., Mandelkow, E., Waldmann, H., & Mandelkow, E.
Affiliations
  • TU Dortmund University (DE)
  • Deutsches Elektronen-Synchrotron DESY (DE)
  • Technische Universität Darmstadt (DE)
Corresponding author
Bulic, Bruno
Venue
Angewandte Chemie International Edition
Publisher
Wiley
Published
2009-02-17
Volume
48
Issue
10
Pages
1740-1752
ISSN
  • 1433-7851 (ISSN-L)
  • 1521-3773
OpenAlex
W2042485050
Cited by
286
References
94
Citations by year
2026: 8 · 2025: 11 · 2024: 17 · 2023: 8 · 2022: 14 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 17 · 2017: 10 · 2016: 14 · 2015: 18 · 2014: 12 · 2013: 27 · 2012: 14
FWCI
2.96
Type
journal article
Language
en
Open access
closed
Locations
  • Angewandte Chemie International Edition (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
tau aggregation inhibitors, Alzheimer's disease, tauopathy, tau aggregation, neurofibrillary tangles, amyloid fibrils, protein misfolding, small molecule inhibitors, MTC, disease-modifying drugs, medicinal chemistry
MeSH terms
Alzheimer Disease, Amyloid, Humans, Thiazoles, Databases, Factual, Amyloid beta-Peptides, tau Proteins, Tauopathies, Benzothiazoles

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