Engineered Clostridium butyricum-pMTL007-GLP-1 Delays Neurodegeneration in Prnp-SNCA*A53T Transgenic Mice Model by Suppressing Astrocyte Senescence.

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butyricum-GLP-1 crossed the blood-brain barrier and bound to GLP-1 receptors, reducing the build-up of senescent astrocytes, as evidenced by increased expression of Lamin B1, decreased levels of the senescence biomarker p21, and decreased levels of the pro-inflammatory senescence-associated secretory phenotype. Moreover, C. 16S rRNA analysis indicated that C. butyricum-GLP-1 strengthened the gastrointestinal barrier, restored gut microbiota homeostasis, and upregulated the abundance of C. In summary, the results of this study suggested that C. butyricum-GLP-1 inhibited p53/p21 pathway, mitigated oxidative stress by targeting astrocyte senescence, and regulated gut microbiota, suggesting it may represent a therapeutic approach that brings renewed hope to patients with age-related diseases, such as Parkinson disease.

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