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  • Title: High expression of the HMGB1-TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging.
    Author: Yang Y, Han C, Guo L, Guan Q.
    Journal: Brain Behav; 2018 Apr; 8(4):e00948. PubMed ID: 29670828.
    Abstract:
    OBJECTIVE: To detect the expression of high-mobility group box protein 1 (HMGB1) and toll-like receptor 4 (TLR4) and their downstream signaling factors-myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α)-in the sera of patients with Parkinson's disease (PD) in order to evaluate the relationship of the HMGB1-TLR4 axis with PD development and progression. METHODS: The serum HMGB1 and TLR4 protein levels of 120 patients with PD and 100 healthy volunteers were measured using double-antibody sandwich ELISA, and their correlations with PD staging, disease duration, drug treatment effectiveness, and clinical classification were analyzed. In addition, their correlations with the key downstream factors of the HMGB1-TLR4 axis (MyD88, NF-κB, and TNF-α) were analyzed. RESULTS: HMGB1 and TLR4 expressions were higher in the peripheral blood of patients with PD than in healthy volunteers. PD patients with poor drug treatment outcomes had significantly higher HMGB1 and TLR4 expressions than PD patients with stable drug treatment outcomes. Higher HMGB1 and TLR4 expressions were found in patients at higher PD stages, and patients with >4-year disease duration had significantly higher HMGB1 and TLR4 expressions than patients with <4-year disease duration. No significant difference in HMGB1 and TLR4 expressions was found among patients with tremor-dominant, akinetic-rigid, and mixed subtypes of PD. NF-κB and TNF-α expressions were positively correlated with high expression of the HMGB1-TLR4 axis. CONCLUSION: High expression of the HMGB1-TLR4 axis is closely associated with PD development, progression, drug treatment effectiveness, staging, and disease duration and has great significance for PD diagnosis and treatment.
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