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. 2018 Mar 25;8(4):e00948.
doi: 10.1002/brb3.948. eCollection 2018 Apr.

High expression of the HMGB1-TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

Yi Yang  1 , Chenyang Han  1 , Li Guo  1 , Qiaobin Guan  1
Affiliations

High expression of the HMGB1-TLR4 axis and its downstream signaling factors in patients with Parkinson's disease and the relationship of pathological staging

Yi Yang et al. Brain Behav. .

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.

Keywords: Parkinson's disease; high‐mobility group box protein 1; myeloid differentiation factor 88; nuclear factor kappa B; toll‐like receptor 4; tumor necrosis factor alpha.

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Figures

Figure 1
Figure 1
Correlation between HMGB1 and TLR4 expressions in the peripheral blood of patients with PD
Figure 2
Figure 2
Relationship between serum HMGB1 and TLR4 expressions and PD staging of patients with PD. (a) Serum HMGB1 expression in patients with PD at different PD stages. Serum HMGB1 expression was increased with increasing PD stages. Significant differences in HMGB1 expression were found among different PD stages (p < .05). (b) Serum TLR4 expression in patients with PD at different PD stages. Serum TLR4 expression was increased with increasing PD stages. Significant differences in TLR4 expression were found among different PD stages (p < .05)
Figure 3
Figure 3
Expression of the HMGB1–TLR4 axis's downstream factors, MyD88, NF‐κB, and TNF‐α, in the sera of patients with PD
See this image and copyright information in PMC

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