ArticleMolecular neurobiology2017
Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies.
Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- Deubiquitinating Enzymes Ubiquitin-Specific Proteases 7 and 10 Regulate TAU Aggregation.International journal of molecular sciences · 2025Article
- Downregulation of USP9X in the DG Region of the Hippocampus Leads to AD-Like Cognitive Dysfunction in Mice.CNS neuroscience & therapeutics · 2025Article
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- The Multifaceted Roles of BACH1 in Disease: Implications for Biological Functions and Therapeutic Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Evolutionary divergence between homologous X-Y chromosome genes shapes sex-biased biology.Nature ecology & evolution · 2025Article
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Brain injury biomarkers and applications in neurological diseases.Chinese medical journal · 2025Review
- DUBs in Alzheimer's disease: mechanisms and therapeutic implications.Cell death discovery · 2024Review
- Targeting USP11 regulation by a novel lithium-organic coordination compound improves neuropathologies and cognitive functions in Alzheimer transgenic mice.EMBO molecular medicine · 2024Article
- USP9X-mediated deubiquitination of Raptor contributes to autophagy impairment and memory deficits in P301S mice.Cell communication and signaling : CCS · 2024Article
- A Prospective Study on Neural Biomarkers in Patients with Long-COVID Symptoms.Journal of personalized medicine · 2024Article
- ExAD-GNN: Explainable Graph Neural Network for Alzheimer's Disease State Prediction from Single-cell Data.APSIPA Transactions on Signal and Information Processing · 2023Article
- The Role of Ubiquitin-Proteasome System and Mitophagy in the Pathogenesis of Parkinson's Disease.Neuromolecular medicine · 2023Review
- Sexual Dimorphism in Neurodegenerative Diseases and in Brain Ischemia.Biomolecules · 2022Review
- Article
- Deubiquitinating enzymes (DUBs): decipher underlying basis of neurodegenerative diseases.Molecular psychiatry · 2022Review
- Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities.Cell death and differentiation · 2021Review
- One-Year Prospective Study of Plasma Biomarkers From CNS in Patients With Mild Traumatic Brain Injury.Frontiers in neurology · 2021Article
- The BACH1/Nrf2 Axis in Brain in Down Syndrome and Transition to Alzheimer Disease-Like Neuropathology and Dementia.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Public transcriptomic studies have shown that several genes display pronounced gender differences in their expression in the human brain, which may influence the manifestations and risk for neuronal disorders. Here, we apply a transcriptome-wide analysis to discover genes with gender-specific expression and significant alterations in public postmortem brain tissue from Alzheimer's disease (AD) patients compared to controls. We identify the sex-linked ubiquitin-specific peptidase 9 (USP9) as an outstanding candidate gene with highly significant expression differences between the genders and male-specific underexpression in AD. Since previous studies have shown that USP9 can modulate the phosphorylation of the AD-associated protein MAPT, we investigate functional associations between USP9 and MAPT in further detail. After observing a high positive correlation between the expression of USP9 and MAPT in the public transcriptomics data, we show that USP9 knockdown results in significantly decreased MAPT expression in a DU145 cell culture model and a concentration-dependent decrease for the MAPT orthologs mapta and maptb in a zebrafish model. From the analysis of microarray and qRT-PCR experiments for the knockdown in DU145 cells and prior knowledge from the literature, we derive a data-congruent model for a USP9-dependent regulatory mechanism modulating MAPT expression via BACH1 and SMAD4. Overall, the analyses suggest USP9 may contribute to molecular gender differences observed in tauopathies and provide a new target for intervention strategies to modulate MAPT expression.
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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.