The Role of Pathway-Driven Neuro-Immune-Programmed Cell DeathInteractive Network in Intervertebral Disc Degeneration
ZHANG Yanjun1*, GUO Jie2, LEI Ling2
IVDD (intervertebral disc degeneration) is a critical pathological basis of chronic low back pain.Its onset and progression involve mechanical damage, inflammatory responses, immune imbalance, and multipleprogrammed cell death processes. Recent studies have shown that the TLR4/NF-κB inflammatory signaling network can promote NLRP3 inflammasome activation, oxidative stress, and ferroptosis, and jointly participate inthe regulation of PANoptosis together with apoptosis, necroptosis, and pyroptosis. DAMPs (damage-associatedmolecular patterns) and inflammatory cytokines generated by cell death further induce immune activation, neuralsensitization, and aberrant neurovascular ingrowth, forming a vicious cycle that facilitates IVDD progression. Inlight of these mechanisms, TLR4/NF-κB, NLRP3, GPX4, and neuroinflammation-related pathways have emergedas potential therapeutic targets. With the development of exosome- and hydrogel-based delivery systems as wellas multi-omics technologies, future IVDD therapy is expected to shift from single-target regulation to multidimensional network intervention, offering new directions for disease-modifying treatment.
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