ArticleAutophagy2021
Modulating FKBP5/FKBP51 and autophagy lowers HTT (huntingtin) levels.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Mechanical loading primes MSC-derived exosomes to promote cartilage repair.Bioactive materials · 2026Article
- FKBP10 may affect the malignant phenotype of oral squamous cell carcinoma cells through the ECM/WNT signaling pathway.Scientific reports · 2026Article
- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
- FKBP51: A new target for Parkinson's disease.Neural regeneration research · 2026Article
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Targeting UCHL3 attenuates pathological markers in neuronal models of Huntington's disease.Brain : a journal of neurology · 2026Article
- Design and In Vitro Evaluation of Cyclodextrin-Functionalized Albumin Nanoparticles for Intranasal Carbamazepine Brain Delivery.Pharmaceutics · 2026Article
- Transcriptional responses to proteotoxic stressors are profoundly diverse and tissue-specific.Cell stress & chaperones · 2026Article
- Rare and novel genetic variants in sporadic and familial Alzheimer's disease: insights from the first Saudi cohort.Frontiers in aging · 2026Article
- Unraveling Complex Interactions Mechanisms Linking PTSD and Chronic Diseases.Current neuropharmacology · 2026Review
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- FK506‑binding proteins as emerging bridges linking proteostasis to multi‑system pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Inhibition of UBE2N promotes the clearance of mutant HTT (huntingtin) in HD knock-in mice.Autophagy · 2025Article
- FKBP5 Regulates Osteogenesis of Human iPSC-Derived Mesenchymal Stem Cells via FKBP5-AKT-FOXO1 Pathway.Journal of cellular and molecular medicine · 2025Article
- Review
- Article
- FKBP5 Induces Senescence in BMSCs and Inhibits Osteogenic Differentiation Through the Canonical WNT/β-Catenin Signalling Pathway in Senile Osteoporosis.Journal of cellular and molecular medicine · 2025Article
- FKBP51 inhibition ameliorates neurodegeneration and motor dysfunction in the neuromelanin-SNCA mouse model of Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Modulation of autophagy by melatonin and its receptors: implications in brain disorders.Acta pharmacologica Sinica · 2025Review
- Small molecule modulation of p75Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Current disease-modifying therapies for Huntington disease (HD) focus on lowering mutant HTT (huntingtin; mHTT) levels, and the immunosuppressant drug rapamycin is an intriguing therapeutic for aging and neurological disorders. Rapamycin interacts with FKBP1A/FKBP12 and FKBP5/FKBP51, inhibiting the MTORC1 complex and increasing cellular clearance mechanisms. Whether the levels of FKBP (FK506 binding protein) family members are altered in HD models and if these proteins are potential therapeutic targets for HD have not been investigated. Here, we found levels of FKBP5 are significantly reduced in HD R6/2 and zQ175 mouse models and human HD isogenic neural stem cells and medium spiny neurons derived from induced pluripotent stem cells. Moreover, FKBP5 interacts and colocalizes with HTT in the striatum and cortex of zQ175 mice and controls. Importantly, when we decreased FKBP5 levels or activity by genetic or pharmacological approaches, we observed reduced levels of mHTT in our isogenic human HD stem cell model. Decreasing FKBP5 levels by siRNA or pharmacological inhibition increased LC3-II levels and macroautophagic/autophagic flux, suggesting autophagic cellular clearance mechanisms are responsible for mHTT lowering. Unlike rapamycin, the effect of pharmacological inhibition with SAFit2, an inhibitor of FKBP5, is MTOR independent. Further,
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Registered trials
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