Traditional Chinese Medicine Regulation of the NLRP3 Inflammasome in Parkinson’s Disease: An Integrative Framework Based on Fuxie Theory

Abstract

Parkinson’s disease (PD) has an insidious onset and a relentlessly progressive course. Abnormal α-synuclein (α-Syn) accumulation, impaired mitochondrial quality control, and sustained NLRP3 inflammasome activation reinforce one another and together constitute the pathological basis of chronic progression. In traditional Chinese medicine (TCM), Fuxie theory describes a dynamic disease course in which pathogenic factors remain concealed, erupt once triggered, and then persist. This temporal logic maps onto the progression of PD from inflammasome priming through activation to feedback amplification. Focusing on these three stages, we review the evidence linking α-Syn burden, Parkin-dependent mitochondrial quality control, ASC specks, and gasdermin D to sustained NLRP3 activity. Without equating TCM pathogenesis with any single molecular mechanism, we propose a Fuxie–NLRP3 integrative framework in which declining quality control, accumulating danger signals, and persistent NLRP3 activation form a candidate mechanistic bridge between deficient healthy qi and sustained neuroinflammation. We then appraise the evidence for Chinese herbal formulas, bioactive compounds, and acupuncture as NLRP3-directed interventions in PD. The framework converts the temporal logic of Fuxie theory into testable mechanistic questions; however, current evidence remains largely correlational and requires stronger causal validation.