HDAC11 displays neuropathological alterations and offers as a novel drug target for Alzheimer's disease
Histone deacetylase-11 (HDAC11) is significantly upregulated in Alzheimer's disease (AD) brains and colocalizes with amyloid pathology and neuroinflammatory markers. Novel brain-permeable HDAC11-selective inhibitor PB94 demonstrates promising therapeutic potential for AD treatment. PB94 treatment reduces amyloid burden and neuroinflammation in AD mouse models, confirmed by live imaging studies. HDAC11 inhibition enhances microglial phagocytosis of amyloid beta proteins and modulates inflammatory cytokine levels. PB94 treatment improves cognitive function in AD mouse models while showing favorable brain penetration and selectivity.
Authors
- Liuyue Yang (ORCID: https://orcid.org/0000-0002-2372-4410)
- Prasenjit Mondal (ORCID: https://orcid.org/0000-0003-0767-449X)
- Changning Wang (ORCID: https://orcid.org/0000-0002-2076-4193)
- Haoqi Sun (ORCID: https://orcid.org/0000-0002-5041-8312)
- Claire Suen
- Rudolph E. Tanzi (ORCID: https://orcid.org/0000-0002-7032-1454)
- Ping Bai (ORCID: https://orcid.org/0000-0003-4587-8426)
- Biyue Zhu (ORCID: https://orcid.org/0000-0002-7367-7421)
- Ashley Gomm (ORCID: https://orcid.org/0000-0002-4812-5959)
- Chongzhao Ran (ORCID: https://orcid.org/0000-0002-3892-4108)
- Shiqian Shen (ORCID: https://orcid.org/0000-0003-0062-6831)
- Yan Liu (ORCID: https://orcid.org/0000-0002-8581-2571)
- Can Zhang (ORCID: https://orcid.org/0000-0002-4340-5118)
Institutions
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Sichuan University (CN)
- Massachusetts General Hospital (US)
- Athinoula A. Martinos Center for Biomedical Imaging (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1002/alz.14616
- Citations
- 3
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.49
Funders
- Cure Alzheimer's Fund
- National Institutes of Health