JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T ?-Syn Mouse Model via PI3K/AKT/GSK-3?

Author(s): Xin FANG^1, ^3, ^5, ^6, , Yun WANG^1, ^3, ^5, ^6, , Zhenli LONG⁴, Bin LIAO^1, ^3, ^5, ^6, , Bo WANG^1, ^3, ^5, ^6, , Daojun HONG^1, ^3, ^5, ^6, , Jie LUO⁷, Tingtao CHEN^1, ²
Affiliation(s): ¹Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; more
Corresponding email(s): jieluo@ncu.edu.cn, chentingtao1984@163.com
Key Words: Parkinson's disease; Clostridium butyricum-pMTL007-GLP-1; Glucagon-like peptide-1 (GLP-1); Gut microbiota; PI3K/AKT/GSK-3? pathway

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Xin FANG^1,^3,^5,^6,, Yun WANG^1,^3,^5,^6,, Zhenli LONG⁴, Bin LIAO^1,^3,^5,^6,, Bo WANG^1,^3,^5,^6,, Daojun HONG^1,^3,^5,^6,, Jie LUO⁷, Tingtao CHEN^1,². Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T ?-Syn Mouse Model via PI3K/AKT/GSK-3?[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/0.1631/jzus.B2500237

@article{title="Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T ?-Syn Mouse Model via PI3K/AKT/GSK-3?",
author="Xin FANG^1,^3,^5,^6,, Yun WANG^1,^3,^5,^6,, Zhenli LONG⁴, Bin LIAO^1,^3,^5,^6,, Bo WANG^1,^3,^5,^6,, Daojun HONG^1,^3,^5,^6,, Jie LUO⁷, Tingtao CHEN^1,²",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/0.1631/jzus.B2500237"
}

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doi="https://doi.org/0.1631/jzus.B2500237"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder with limited therapeutic options and no cure, underscoring the urgent need for novel treatment strategies. Our previous work demonstrated that an engineered strain of Clostridium butyricum-pMTL007-GLP-1 (C. butyricum-GLP-1) alleviated PD symptoms by enhancing mitophagy, though the exact molecular mechanisms remained incompletely understood. Methods: In this study, we further investigated the neuroprotective effects and underlying mechanisms of this engineered strain using an A53T ?-synuclein transgenic mouse model of PD. Specifically, we evaluated its impact on motor function, gut ?-synuclein expression, intestinal barrier function, gut microbial composition, and neuropathological changes, with a focus on the PI3K/AKT/GSK-3? signaling pathway. Results: Our findings revealed that C. butyricum-GLP-1 ameliorated motor deficits in PD mice by reducing intestinal ?-synuclein accumulation, restoring gut barrier function, and modulating microbial diversity�notably increasing the relative abundance of of Prevotella at the genus level. Furthermore, the engineered strain attenuated neuropathological alterations by decreasing phosphorylated ?-synuclein (p-?-syn) in the substantia nigra while upregulating tyrosine hydroxylase (TH), dopamine-transporter (DAT), and glucagon-like peptide-1-receptor (GLP-1R) expression. These neuroprotective effects were associated with suppressed proinflammatory responses and enhanced anti-inflammatory and anti-apoptotic signaling, likely mediated through PI3K/AKT/GSK-3? pathway activation. Conclusions: C. butyricum-pMTL007-GLP-1 exerts significant neuroprotective effects in PD mice by reshaping gut microbiota composition and activating the PI3K/AKT/GSK-3? pathway. These findings provide further theoretical support for the potential application of probiotic-based therapies in Parkinson’s disease treatment.

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