Depression is a debilitating mental disease that inflicts significant harm upon individuals and society, yet effective treatment options remain elusive. At present, the pathogenesis of multiple depression is not fully clear, but its occurrence can be related to biological or environmental pathways, among which Brain-derived neurotrophic factor (BDNF) can unequivocally act on two downstream receptors, tyrosine kinase receptor (TrkB) and the p75 neurotrophin receptor (p75NTR), then affect the related signal pathways, affecting the occurrence and development of depression. Accumulating studies have revealed that BDNF-related pathways are critical in the pathophysiology of depression, and their interaction can further influence the efficacy of depression treatment. In this review, we mainly summarized the signaling pathways associated with BDNF and classified them according to different receptors and related molecules, providing promising insights and future directions in the treatment of depression.

Myocardial ischemia-reperfusion injury (MIRI) constitutes an essential hurdle following reperfusion therapy for acute myocardial infarction (AMI), which the mechanism involves oxidative stress, inflammatory response, calcium overload, and ferroptosis, etc. MAQAAEYYR (P2), a kind of marine-derived bioactive peptide from C-Phycocyanin (C-PC), exhibits remarkable antioxidant properties. Due to its low molecular weight, P2 exhibits superior bioavailability compared to C-PC. A previous study has confirmed that C-PC could alleviate ischemia-reperfusion (I/R)-induced cardiac dysfunction. However, whether the peptide derived from C-PC has the potential to protect the heart against ischemia-reperfusion injury deserves consideration and investigation. In this study, C57BL/6 male mice and H9C2 cardiomyocytes were used to construct myocardial ischemia-reperfusion (MI/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) injury models in vivo and in vitro respectively. We demonstrated that P2 significantly improved myocardial function, myocardial enzymes, myocardial fibrosis, and mitochondrial ultrastructure, while mitigating oxidative stress damage and ferroptosis caused by MI/R. In vitro, P2 markedly enhanced cell viability, suppressed the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), elevated glutathione (GSH) and superoxide dismutase (SOD) levels, and prevented the occurrence of ferroptosis. Furthermore, we revealed that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) knockdown reversed the protective effect of P2 against OGD/R-induced cardiomyocyte ferroptosis. This study demonstrated that P2 protects the myocardium against ischemia-reperfusion injury and mitigates ferroptosis by upregulating UCHL3. It provides a foundation for the potential application prospects of marine-derived bioactive peptides in cardiovascular disease management.