Novel Regulatory Cell Death in Intervertebral Disc Degeneration

Area of Science:

• Biomedical Science
• Cell Biology
• Pathology

Background:

• Intervertebral disc degeneration (IDD) is a complex condition causing chronic low back pain, involving cellular dysfunction and matrix degradation.
• Programmed cell death (PCD), particularly apoptosis and autophagy, has been traditionally linked to IDD.
• Recent research highlights emerging forms of regulated cell death (RCD) as critical players in IDD pathogenesis.

Purpose of the Study:

• To systematically review five emerging RCD modalities (ferroptosis, cuproptosis, necroptosis, PANoptosis, disulfidptosis) in the context of IDD.
• To elucidate their mechanistic roles, regulatory factors, signaling pathways, and interactions in disc degeneration.
• To explore RCD-targeted therapeutic strategies for IDD.

Main Methods:

• Systematic review of current literature on emerging RCD modalities and their involvement in IDD.
• Analysis of mechanistic roles, key regulatory factors, and signaling pathways.
• Evaluation of potential therapeutic interventions targeting RCD.

Main Results:

• Emerging RCD modalities like ferroptosis, cuproptosis, necroptosis, PANoptosis, and disulfidptosis are key drivers of IDD.
• These RCD pathways interact and converge on shared nodes (oxidative stress, mitochondrial dysfunction, inflammation), amplifying cell loss and matrix destruction.
• Pharmacological approaches targeting RCD (e.g., iron chelators, antioxidants) show therapeutic potential for IDD.

Conclusions:

• Emerging RCD mechanisms provide a comprehensive framework for understanding IDD pathology.
• Targeting RCD offers a basis for developing multi-target, disease-modifying interventions for IDD.
• Future research needs to address spatiotemporal dynamics and interactions of RCD in different degeneration stages for precision treatment.