Targeting the ferroptosis crosstalk:novel alternative strategies for the treatment of major depressive disorder

Depression is a major contributor to poor global health and disability,with a recently increasing incidence.Although drug therapy is commonly used to treat depression,conventional antidepressant drugs have several disadvantages,including slow onset,low response rates and severe adverse effects.Therefore,developing effective therapies for depression remains challenging.Although various aetiological theories of depression exist,the underlying mechanisms of depression are complex,and further research is crucial.Moreover,oxidative stress(OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis.Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders,and investigation of the mediators involved in these processes has emerged as a prominent and active research direction.One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression,and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis in vivo,suggesting an important role of ferroptosis in the pathogenesis of depression.Hence,our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved,specifically concerning ferroptosis and OS in the context of depression,along with promising prospects for using molecular mediators to target ferroptosis.We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression,most notably reactive oxygen species and iron overload.Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders,delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.

The antiferroptotic role of TRIM7:Molecular mechanism and synergistic effect with temozolomide

Ferroptosis is a distinct form of regulated cell death characterized by the accumulation of lipid peroxides and iron-dependent membrane damage that is a significant contributor to drug resistance in glioblastoma(GBM).Dysregulated iron metabolism is a hallmark of cancer,making ferroptosis a unique potential target for anticancer therapy.Ferritinophagy,the selective autophagy of ferritin,plays an essential role in cellular iron homeostasis and may impact the vulnerability of cells to ferroptosis.Nuclear receptor coactivator 4(NCOA4)protein is a selective cargo receptor that plays a crucial role in ferritinophagy by targeting and delivering the ferritin iron storage protein to the lysosome for degradation,releasing iron[1].However,the underlying molecular mechanism that causes reduced NCOA4 expression in glioma is not fully understood.

An integrated analysis of C5AR2 related to malignant properties and immune infiltration of gliomas

Background:C5AR2 is recognized as a proinflammatory molecule and activates the inflammatory response in multiple disorders.However,little has been reported on C5AR2 in glioma.This study sought to explore its expression,biological function,and association with clinical pathological indicators,prognosis,and immune infiltration levels in glioma through glioma cohorts.Methods:A cohort of 657 patients was screened from the Chinese Glioma Genome Atlas(CGGA).χ^(2) test was performed to calculate the difference of classified variables.Cox proportional hazard regression modeling was used to identify independent prognostic indicators of glioma patients.A survival plot was generated by the Kaplan–Meier method.The immune cell infiltration score of glioma patients was calculated by TIMER algorithm.Results:We observed that high expression of C5AR2 was strongly associated with malignant clinical indicators in 657 patients with glioma,and patients with high C5AR2 expression had worse prognoses.Multivariate Cox analysis showed that C5AR2 could be a new independent prognostic indicator for glioma patients.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that C5AR2 overexpression correlated with multiple inflammatory and immune biological processes.Additionally,high C5AR2 expression was strongly associated with higher abundance and marker gene expression of multiple tumor immune cells in low-grade glioma.Finally,a model was constructed to improve the prognostic evaluation of glioma patients.Conclusions:The C5AR2 gene is highly expressed in gliomas and is significantly associated with clinical indicators of malignant progression in glioma patients.In glioma,patients with high C5AR2 expression displayed a worse outcome.In glioma tissues,the expression level of C5AR2 highly correlated with the abundance of tumor immune cell infiltration.Additionally,GO and KEGG enrichment analysis revealed that C5AR2 expression may be involved in a variety of immune and inflammatory biological processes.