ArticleCell chemical biology2017
Selectivity and Kinetic Requirements of HDAC Inhibitors as Progranulin Enhancers for Treating Frontotemporal Dementia.
Article in Cell chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia.The Journal of clinical investigation · 2019Trial
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Isoform-specific vs. pan-histone deacetylase inhibition as approaches for countering glioblastoma: anFrontiers in oncology · 2025Article
- Epigenetic regulation-mediated disorders in dopamine transporter endocytosis: A novel mechanism for the pathogenesis of Parkinson's disease.Theranostics · 2025Review
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
- Epigenetic modulation through BET bromodomain inhibitors as a novel therapeutic strategy for progranulin-deficient frontotemporal dementia.Scientific reports · 2024Article
- Progranulin is an FMRP target that influences macroorchidism but not behaviour in a mouse model of Fragile X Syndrome.Current research in neurobiology · 2023Article
- Genes for RNA-binding proteins involved in neural-specific functions and diseases are downregulated in Rubinstein-Taybi iNeurons.Neural regeneration research · 2022Article
- Histone Modifications in Neurological Disorders.Advances in experimental medicine and biology · 2022Review
- Differentiation of Human Induced Pluripotent Stem Cells into Cortical Neurons to Advance Precision Medicine.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.Neuromolecular medicine · 2021Review
- Evaluation of Class IIa Histone Deacetylases Expression and In Vivo Epigenetic Imaging in a Transgenic Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2021Article
- Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease.Frontiers in neurology · 2021Review
- Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration.Journal of experimental pharmacology · 2021Review
- Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities.Frontiers in molecular neuroscience · 2021Review
- Protein acetylation and deacetylation: An important regulatory modification in gene transcription (Review).Experimental and therapeutic medicine · 2020Review
- Human pluripotent stem cell-derived models and drug screening in CNS precision medicine.Annals of the New York Academy of Sciences · 2020Review
- Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA).Molecular and cellular neurosciences · 2019Article
- Kinetic Tuning of HDAC Inhibitors Affords Potent Inducers of Progranulin Expression.ACS chemical neuroscience · 2019Article
- Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response.PLoS genetics · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Frontotemporal dementia (FTD) arises from neurodegeneration in the frontal, insular, and anterior temporal lobes. Autosomal dominant causes of FTD include heterozygous mutations in the GRN gene causing haploinsufficiency of progranulin (PGRN) protein. Recently, histone deacetylase (HDAC) inhibitors have been identified as enhancers of PGRN expression, although the mechanisms through which GRN is epigenetically regulated remain poorly understood. Using a chemogenomic toolkit, including optoepigenetic probes, we show that inhibition of class I HDACs is sufficient to upregulate PGRN in human neurons, and only inhibitors with apparent fast binding to their target HDAC complexes are capable of enhancing PGRN expression. Moreover, we identify regions in the GRN promoter in which elevated H3K27 acetylation and transcription factor EB (TFEB) occupancy correlate with HDAC-inhibitor-mediated upregulation of PGRN. These findings have implications for epigenetic and cis-regulatory mechanisms controlling human GRN expression and may advance translational efforts to develop targeted therapeutics for treating PGRN-deficient FTD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.