fig4

Figure 4. Conceptual framework illustrating how MSC-EVs may intercept convergent signalling pathways associated with post-viral infection neurodegenerative risk. Viral infections such as SARS-CoV-2 can generate a prolonged CNS stress state characterised by neuroinflammation with BBB dysfunction, mitochondrial and redox imbalance, and impaired proteostasis with declining trophic support. These interrelated vulnerability nodes may predispose virus-exposed neural tissue to neurodegenerative response. MSC-EV: Mesenchymal stem cell-derived extracellular vesicle; CNS: central nervous system; BBB: blood-brain barrier; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; STAT3: signal transducer and activator of transcription 3; NLRP3: NOD-like receptor family pyrin domain containing 3; BDNF: brain-derived neurotrophic factor; GDNF: glial cell line-derived neurotrophic factor; IGF-1: insulin-like growth factor 1; VEGF: vascular endothelial growth factor; Ang-1: angiopoietin-1; MMP-2/9: matrix metalloproteinase 2/9; ZO-1: zonula occludens-1; HIF-1α: hypoxia-inducible factor 1 alpha; KEAP1: Kelch-like ECH-associated protein 1; NRF2: nuclear factor erythroid 2-related factor 2; ARE: antioxidant response element; OXPHOS: oxidative phosphorylation; ER: endoplasmic reticulum.