Melatonin's Regulatory Influence on Pyroptosis: Biological Characteristics and Therapeutic Potentials

Area of Science:

• Biochemistry
• Cell Biology
• Pathology

Background:

• Pyroptosis, a pro-inflammatory programmed cell death (PCD), is implicated in numerous diseases.
• Melatonin is a pleiotropic regulator with demonstrated anti-pyroptotic effects in preclinical models.
• A systematic review of melatonin's mechanistic role in pyroptosis across organ systems is lacking.

Purpose of the Study:

• To systematically review the molecular mechanisms of melatonin's regulation of pyroptosis.
• To elucidate melatonin's inhibitory effects on inflammasome activation, particularly the NLRP3 pathway.
• To comparatively assess therapeutic evidence for melatonin in pyroptosis-related pathologies.

Main Methods:

• Systematic literature review and analysis of preclinical studies.
• Elucidation of molecular pathways including TLR4/NF-κB, SIRT3/FOXO3α, and Nrf2 signaling.
• Comparative assessment of melatonin's efficacy in cardiovascular, neurological, renal, hepatic, pulmonary, and obstetric disorders.

Main Results:

• Melatonin inhibits pyroptosis via multiple signaling pathways, including TLR4/NF-κB, SIRT3/FOXO3α, and Nrf2.
• Specific focus on melatonin's suppression of NLRP3 inflammasome activation.
• Evidence supports melatonin's therapeutic role in mitigating pyroptosis-associated conditions in diverse organ systems.

Conclusions:

• Melatonin acts as a targeted modulator of pyroptosis through defined molecular mechanisms.
• Melatonin demonstrates significant therapeutic potential for pyroptosis-related diseases.
• Further translational research is warranted to explore melatonin's clinical applications.