PHARMACOLOGICAL MODULATION OF NLRP3 INFLAMMASOME–MEDIATED NEUROINFLAMMATORY PATHWAYS IN EXPERIMENTAL PARKINSONIAN MODELS: A SYSTEMATIC REVIEW AND META-ANALYSIS

Background: The NLRP3 inflammasome has been implicated in neuroinflammatory pathways associated with Parkinson's disease (PD) (Gordon et al., 2018). This systematic review and meta-analysis evaluated the effects of direct pharmacological NLRP3 inhibition in experimental rodent models of PD. Methods: PubMed/MEDLINE, Embase, and Web of Science Core Collection were searched for controlled in vivo rodent studies investigating direct small-molecule NLRP3 inhibitors. Risk of bias was assessed using the SYRCLE tool. Standardized mean differences were expressed as Hedges' g and pooled using random-effects models. Results: Three publications comprising four experimental cohorts, all evaluating MCC950, were included. The pooled estimates favored MCC950 for substantia nigra pars compacta tyrosine hydroxylase-positive (TH-positive) neuronal outcomes (Hedges' g = 3.18; 95% CI, 1.98–4.38), rotarod performance (Hedges' g = 2.76; 95% CI, 1.90–3.63), and midbrain mature interleukin-1β (IL-1β) levels (Hedges' g = −4.28; 95% CI, −5.32 to −3.23). Conclusion: These findings suggest that NLRP3 inhibition may improve dopaminergic, inflammatory, and motor outcomes in experimental PD models. The limited number of publications and reliance on MCC950 warrant further investigation across independent studies and pharmacological agents.