Endo-Lysosomal and Autophagy Pathway and Ubiquitin-Proteasome System in Mood Disorders: A Review Article

Mood disorders are disabling conditions that cause significant functional impairment. Due to the clinical heterogeneity and complex nature of these disorders, diagnostic and treatment strategies face challenges. The etiology of mood disorders is multi-factorial, involving genetic and environmental aspects that are associated with specific biological pathways including inflammation, oxidative stress, and neuroprotection. Alterations in these pathways may reduce the cell's ability to recover from stress conditions occurring during mood episodes. The endo-lysosomal and autophagy pathway (ELAP) and the ubiquitin-proteasome system (UPS) play critical roles in protein homeostasis, impacting neuroplasticity and neurodevelopment. Thus, emerging evidence has suggested a role for these pathways in mental disorders. In the case of neurodegenerative diseases (NDDs), a deeper understanding in the role of ELAP and UPS has been critical to discover new treatment targets. Since it is suggested that NDDs and mood disorders share clinical symptomatology and risk factors, it has been hypothesized that there might be common underlying molecular pathways. Here, we review the importance of the ELAP and UPS for the central nervous system and for mood disorders. Finally, we discuss potential translational strategies for the diagnosis and treatment of major depressive disorder and bipolar disorder associated with these pathways.