Publication date: Jun 24, 2025
Depression is one of the most common and debilitating mental disorders and one of the main causes of disability worldwide. Despite the progress made in the treatment of depression, approximately 20 %-40 % of patients with a major depressive episode do not show a clinical response to current antidepressant treatments. Approximately 85 % of patients with major depressive disorder (MDD) experience a high relapse rate after recovering from an acute episode of major depression. Over the past decade, protein ubiquitination and deubiquitination have attracted considerable interest. An increasing number of studies have shown that ubiquitin-specific proteases (USPs) play essential roles in the pathogenesis of depression. USP is part of the ubiquitin-proteasome system (UPS), a critical non-lysosomal pathway specific for protein degradation, and plays a significant role in presynaptic and postsynaptic proteins crucial for regulating neurotransmission and synaptic plasticity. However, its potential contribution to the pathophysiology of depression has not yet been addressed in detail. Therefore, this review explores the potential of targeting USP as a novel approach to antidepressant treatment, focusing on the targets and mechanisms of USP in the regulation of depression. By providing insights into USP in preclinical research, this review aims to contribute to developing new therapeutic methods for enhancing the efficacy of antidepressant treatments.
| Concepts | Keywords |
|---|---|
| Biochem | Antidepressant-like effects |
| Decade | Depression |
| Pharmacol | Mechanisms |
| Relapse | Neurogenesis |
| Ubiquitin | Ubiquitin-specific proteases |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | depression |
| disease | MESH | mental disorders |
| disease | MESH | causes |
| disease | MESH | major depressive disorder |
| disease | MESH | relapse |
| pathway | REACTOME | Protein ubiquitination |
| pathway | REACTOME | Deubiquitination |
| pathway | KEGG | Proteasome |