The role and advance of ubiquitination and deubiquitination in depression pathogenesis and treatment

Abstract Depression is a common neuropsychiatric disease that is characterized by long‐term, repeated low mood, pain and despair, pessimism, and even suicidal tendencies. Increasing evidence has shown that ubiquitination and deubiquitination are closely related to the occurrence of depression, including pathological morphogenesis, neuroplasticity, synaptic transmission, neuroinflammation, and so forth. The development of depression is regulated by intracellular proteins that undergo various posttranslational modifications, including ubiquitination, which falls under the epigenetics category. Although there have been studies and reviews of literature on epigenetics and depression, a systematic review of ubiquitination modification and depression has not been reported. In addition, with the deepening of research on depression and ubiquitination, the development of drugs targeting the ubiquitin system has gradually increased, but it is still not mature, so there is an urgent need to find new antidepressant drug targets. E3 ubiquitin ligases and deubiquitinating enzymes can regulate the occurrence and development of depression in a variety of ways, which may be a direction for the treatment of depression in the future. Therefore, this review describes the latest progress of ubiquitination and deubiquitination in the regulation of depression, summarizes the published signal pathways of ubiquitination and deubiquitination involved in depression, emphasizes the targets and mechanisms of E3 ubiquitin ligases and deubiquitinase in the regulation of depression, and further discusses the therapeutic targets of targeting ubiquitination modification systems to regulate depression.