A phenotypic screen for novel small molecules that correct tau‐mediated pathologies in human frontotemporal dementia neurons
A phenotypic screen for novel small molecules that suppress tau-mediated pathologies was carried out in human frontotemporal dementia neurons. The key readout was correction of nuclear membrane defects, which are a pathological feature in tauopathies in vivo. The screen of 20,000 small molecules identified more than 20 compounds that corrected the phenotype in a dose-dependent manner. Hit compounds commonly altered microtubules, with a subset changing tau protein levels or phosphorylation.
Authors
- Hillary Maxwell (ORCID: https://orcid.org/0000-0002-0988-0206)
- Tom Campbell (ORCID: https://orcid.org/0000-0001-8515-3695)
- Francesco Paonessa (ORCID: https://orcid.org/0000-0002-4729-0928)
- Peter R. Maycox
- Mark L. Evans (ORCID: https://orcid.org/0000-0001-8122-8987)
- James Smith (ORCID: https://orcid.org/0000-0001-9131-5849)
- Rick Livesey (ORCID: https://orcid.org/0000-0001-6128-3372)
- Sergey Sitnikov
- J. B. Clark
- Rosanna La Rocca
Institutions
- Mission Therapeutics (United Kingdom) (GB)
- Takeda (United Kingdom) (GB)
- Takeda (Japan) (JP)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1002/alz.70620
- Citations
- 1
- Primary Topic
- Nuclear Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Takeda Pharmaceutical Company