ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Structure-Based Discovery of A Small Molecule Inhibitor of Histone Deacetylase 6 (HDAC6) that Significantly Reduces Alzheimer's Disease Neuropathology.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Towards Structural Restoration: Epigenetic Reprogramming and Direct Astrocyte-to-Neuron Lineage Conversion as Next-Generation Regenerative Neurotherapeutics.Molecular neurobiology · 2026Review
- HDAC11 as a potential therapeutic target for Alzheimer's disease.Drug discovery today · 2026Review
- The neuroprotective effect of Cucurbitacin B against Aβ and tau toxicities requires functional HDAC6 and stress granule pathways.Biogerontology · 2026Article
- Decoding unchanged transcriptome of Alzheimer's disease reveals an NCAM1 mRNA switch as a potential biomarker.iScience · 2026Article
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Dynamic single-cell transcriptomics reveals lsamp-guided neural network formation in male S. japonicum driving female reproduction.Nature communications · 2026Article
- Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.Biomolecules · 2026Review
- Beyond apoptosis: Exploring necroptosis, ferroptosis, and pyroptosis in sevoflurane- and isoflurane-associated PNDs.IBRO neuroscience reports · 2025Review
- Review
- Epigenetic regulation of iron metabolism and ferroptosis in Parkinson's disease: Identifying novel epigenetic targets.Acta pharmacologica Sinica · 2025Review
- Histone Deacetylation in Alzheimer's Diseases (AD); Hope or Hype.Cell biochemistry and biophysics · 2025Review
- Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Article
- HDAC11 displays neuropathological alterations and offers as a novel drug target for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The regulatory mechanisms and treatment of HDAC6 in immune dysregulation diseases.Frontiers in immunology · 2025Review
- Editorial: Current chemical approaches in combating neuroinflammation in Alzheimer's disease (AD).Frontiers in aging neuroscience · 2025Article
- Systems pharmacology identifies ajugol-mediated NF-κB/caspase-3 inhibition and isoacteoside-driven p62/mTOR-mediated autophagy as key mechanisms of Rehmanniae Radix and its processed form in Alzheimer's treatment.Frontiers in pharmacology · 2025Article
- Review
- HDAC6 Deletion Decreases Pristane-induced Inflammation.ImmunoHorizons · 2024Article
- Structure-Based Discovery of A Small Molecule Inhibitor of Histone Deacetylase 6 (HDAC6) that Significantly Reduces Alzheimer's Disease Neuropathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Histone deacetylase 6 (HDAC6) is one of the key histone deacetylases (HDACs) that regulates various cellular functions including clearance of misfolded protein and immunological responses. Considerable evidence suggests that HDAC6 is closely related to amyloid and tau pathology, the two primary hallmarks of Alzheimer's disease (AD). It is still unclear whether HDAC6 expression changes with amyloid deposition in AD during disease progression or HDAC6 may be regulating amyloid phagocytosis or neuroinflammation or other neuropathological changes in AD. In this work, the pathological accumulation of HDAC6 in AD brains over age as well as the relationship of its regulatory activity - with amyloid pathogenesis and pathophysiological alterations is aimed to be enlightened using the newly developed HDAC6 inhibitor (HDAC6i) PB118 in microglia BV2 cell and 3D-AD human neural culture model. Results suggest that the structure-based rational design led to biologically compelling HDAC6i PB118 with multiple mechanisms that clear Aβ deposits by upregulating phagocytosis, improve tubulin/microtubule network by enhancing acetyl α-tubulin levels, regulate different cytokines and chemokines responsible for inflammation, and significantly reduce phospho-tau (p-tau) levels associated with AD. These findings indicate that HDAC6 plays key roles in the pathophysiology of AD and potentially serves as a suitable pharmacological target through chemical biology-based drug discovery in AD.
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Registered trials
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