** is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
USP10 is a member of the Ubiquitin Specific Peptidase (USP) family of deubiquitinating enzymes. It contains a conserved catalytic domain with the characteristic Cys, His, and Asp residues that form the catalytic triad. USP10 has a flexible N-terminal domain that regulates its localization and substrate specificity, and a C-terminal domain that contributes to protein-protein interactions.
¶ Domain Architecture
- N-terminal Domain: Positions 1-200 - Regulatory, substrate targeting
- USP Catalytic Domain: Positions 200-600 - Peptidase activity
- DUB Core: Conserved catalytic triad (Cys751, His879, Asp896)
USP10 plays essential roles in neuronal biology:
- p53 Regulation: Deubiquitinates and stabilizes p53 tumor suppressor
- DNA Damage Response: Regulates DNA repair through p53-dependent mechanisms
- Stress Granules: Associates with stress granules under cellular stress
- Autophagy: Modulates autophagic flux through deubiquitination of key regulators
- Synaptic Function: Regulates synaptic protein composition and function
USP10 is widely expressed in neurons and glia throughout the brain, with important functions in maintaining neuronal homeostasis.
USP10 is implicated in AD:
- p53 stability: Loss of USP10 affects neuronal apoptosis regulation
- Amyloid toxicity: Modulates cellular responses to Aβ exposure
- Tau pathology: May influence tau phosphorylation and aggregation
In PD, USP10:
- Alpha-synuclein: Regulates α-synuclein degradation pathways
- Mitochondrial quality control: Affects mitophagy and mitochondrial health
- Dopaminergic neuron survival: Protects against oxidative stress
USP10 involvement in HD:
- Mutant huntingtin: May modulate aggregation and clearance
- Transcriptional regulation: Affects gene expression changes
- Neuronal viability: Loss promotes neuronal death
| Agent |
Mechanism |
Status |
Notes |
| USP10 inhibitors |
Block deubiquitinase activity |
Research |
Anti-cancer applications |
| USP10 activators |
Enhance activity |
Preclinical |
Neuroprotective potential |
| Gene therapy |
Modulate expression |
Research |
AAV delivery explored |
- Yuan et al., USP10 regulates p53 stability (2010)
- Haitao et al., USP10 and autophagy (2015)
- Liu et al., USP10 in neuronal death (2017)