Low-grade chronic inflammatory stimulation alleviates α-syn accumulation in Parkinson’s disease by activating autophagy to promote neuronal survival in the Thy1-h[A30P]α-syn mouse model.

Publication date: Jun 20, 2025

The impact of inflammation on Parkinson’s disease (PD) development and progression varies based on factors such as the intensity, duration of inflammation, and the disease stage. Delving deeper into this aspect could unveil novel therapeutic opportunities for PD treatment. (Thy-1)-h[A30P]α-syn mice were used as PD animal models. Low-grade chronic inflammatory stimulation was applied by the treatment of lipopolysaccharide (LPS) or monophosphoryl lipid (MPL). RT-qPCR, western blotting, IHC, and IF staining were utilized to confirm the relative expression of targeted genes and proteins. Assay kits were used to determine the levels of Cathepsin B (CTSB) activities. The motor function of the mice was assessed by pole-climbing test and field test. Mild inflammatory stimulus activated microglia without elevating their secretion of inflammatory cytokines. This stimulation also induced activation of autophagy, and facilitated the degradation of α-syn in the midbrain by triggering the autophagy-lysosome pathway, thereby fostering neuron survival. Low-grade inflammatory stimulation promoted α-syn degradation via the autophagy-lysosome pathway. These findings offer new perspectives for the treatment of PD.

Concepts Keywords
Inflammatory Parkinson’s disease
Lipopolysaccharide the autophagy-lysosome pathway
Parkinson α‑syn accumulation
Stage
Therapeutic

Semantics

Type Source Name
disease MESH Parkinson’s disease
pathway REACTOME Autophagy
disease MESH inflammation
pathway KEGG Lysosome

Original Article

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