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Peroxiredoxin 6 (PRDX6), the only mammalian 1-Cys member of the peroxiredoxins (PRDXs) family, has multiple functions of glutathione peroxidase (Gpx) activity, acidic calcium-independent phospholipase (aiPLA2) activity, and lysophosphatidylcholine acyl transferase (LPCAT) activity. It has been documented to be involved in redox homeostasis, phospholipid turnover, glycolipid metabolism, and cellular signaling. Here, we reviewed the characteristics of the available Prdx6 genetic mouse models and the research progresses made with regard to PRDX6 in neuropsychiatric disorders, including neurodegenerative diseases, brain aging, stroke, neurotrauma, gliomas, major depressive disorder, drug addiction, post-traumatic stress disorder, and schizophrenia. The present review highlights the important roles of PRDX6 in neuropsychiatric disorders and may provide novel insights for the development of effective pharmacological treatments and genetic therapies. [ABSTRACT FROM AUTHOR]

• The Wistar Kyoto rats may be separated into the depression and non-depression subgroups. • Mice exposed to chronic social defeat stress can be divided into the susceptible and resilient subgroups. • Increased Notch2/NF-κB signaling in the medial prefrontal cortex correlates with the depression susceptibility. • Increased Notch2/NF-κB signaling may provide a potential diagnostic biomarker or therapeutic target for major depressive disorder. The susceptibility to depression has been attributed to the chronic stress and genetic factors but still fails to identify definite biomarkers. The present study aimed to investigate the role of disrupted Notch signaling in the medial prefrontal cortex of the chronic social defeat stress (CSDS) mice and Wistar Kyoto (WKY) rats. RNA-sequencing and quantitative real-time PCR analyses evidenced the involvement of Notch signaling pathway in depression. Western blotting reported an increased level of Notch2 and NF-κB and a decreased level of Hes1 and Bcl2/Bax ratio both in the susceptible mice when compared with the control or resilient ones and in the depression WKY rats when compared with the Wistar or non-depression WKY groups. Further analysis showed that the above-mentioned changes were significantly correlated with the depression-like behaviors and that the elicited Notch2 strongly correlated with the upregulated NF-κB, not with the downregulated Hes1 or Bcl2/Bax ratio. In conclusion, the increased Notch2/NF-κB signaling in the medial prefrontal cortex may mediate depression susceptibility, providing a potential diagnostic biomarker or therapeutic target for treating major depressive disorder. [ABSTRACT FROM AUTHOR]