MECCANISMI INFIAMMATORI NEL PROCESSO NEURODEGENERATIVO DELLA MALATTIA DI PARKINSON: IL RUOLO DI NRF2

Background: Preclinical studies have highlighted the significant role of neuroinflammation, particularly the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, in the pathogenesis of Parkinson's disease (PD). Nrf2 exhibits neuroprotective and anti-inflammatory properties that are potential targets for new therapeutic strategies. Objective: This study aimed to investigate the Nrf2 pathway and its downstream enzyme SOD1 in PD patients to understand their roles in neuroinflammation and neurodegeneration. Additionally, the potential contributions of pro-inflammatory cytokines (TNF-α, IFN-γ, CX3CL1) and neurofilament light chain (NfL) were explored. Methods: The levels of Nrf2 and its downstream effector enzyme SOD1 were measured in peripheral blood mononuclear cells (PBMCs) of PD patients and healthy controls. Additionally, plasma levels of pro-inflammatory cytokines (TNF-α, IFN-γ, CX3CL1) and neurofilament light chain (NfL) were assessed. Biochemical data were correlated with clinical parameters, including motor and non-motor symptoms evaluated using the MDS-UPDRS part III, Montreal Cognitive Assessment (MoCA), and Non-Motor Symptoms Scale (NMSS). Results: No significant differences were found in the levels of Nrf2 and SOD1 in PD patients versus healthy controls, nor between the PD subgroups (de novo, intermediate, advanced-PD). Similarly, plasma levels of TNF-α, IFN-γ, and CX3CL1 did not show significant differences between groups. Clinical assessments showed lower UPDRS III and NMSS scores in earlier PD stages, with similar MoCA scores across all groups. The levels of NfL did not differ significantly between PD patients and controls. Conclusions: Our study did not detect significant changes in Nrf2, SOD1, and pro-inflammatory cytokine levels in PD patients. These preliminary results highlight the complexity of neuroinflammatory mechanisms in PD and the necessity for further research with larger sample sizes and comprehensive methodologies. Despite the challenges, peripheral blood biomarkers remain a promising area for early diagnosis, prognosis, and personalized treatment strategies in PD. Key Words: biomarkers; Nrf2; neuroinflammation; Parkinson’s disease; SOD1; cytokines; neurofilament.