Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T α-Syn Mouse Model via PI3K/AKT/GSK-3β
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Xin FANG1,3,5,6, Yun WANG1,3,5,6, Zhenli LONG4, Bin LIAO1,3,5,6, Bo WANG1,3,5,6, Daojun HONG1,3,5,6, Jie LUO7, Tingtao CHEN1,2. Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T α-Syn Mouse Model via PI3K/AKT/GSK-3β[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .
@article{title="Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T α-Syn Mouse Model via PI3K/AKT/GSK-3β",
author="Xin FANG1,3,5,6, Yun WANG1,3,5,6, Zhenli LONG4, Bin LIAO1,3,5,6, Bo WANG1,3,5,6, Daojun HONG1,3,5,6, Jie LUO7, Tingtao CHEN1,2",
journal="Journal of Zhejiang University Science B",
volume="-1",
number="-1",
pages="",
year="1998",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2500237"
}
%0 Journal Article
%T Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T α-Syn Mouse Model via PI3K/AKT/GSK-3β
%A Xin FANG1
%A 3
%A 5
%A 6
%A Yun WANG1
%A 3
%A 5
%A 6
%A Zhenli LONG4
%A Bin LIAO1
%A 3
%A 5
%A 6
%A Bo WANG1
%A 3
%A 5
%A 6
%A Daojun HONG1
%A 3
%A 5
%A 6
%A Jie LUO7
%A Tingtao CHEN1
%A 2
%J Journal of Zhejiang University SCIENCE B
%V -1
%N -1
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%@ 1673-1581
%D 1998
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2500237
TY - JOUR
T1 - Neuroprotection of Engineered Clostridium butyricum-pMTL007-GLP-1 in A53T α-Syn Mouse Model via PI3K/AKT/GSK-3β
A1 - Xin FANG1
A1 - 3
A1 - 5
A1 - 6
A1 - Yun WANG1
A1 - 3
A1 - 5
A1 - 6
A1 - Zhenli LONG4
A1 - Bin LIAO1
A1 - 3
A1 - 5
A1 - 6
A1 - Bo WANG1
A1 - 3
A1 - 5
A1 - 6
A1 - Daojun HONG1
A1 - 3
A1 - 5
A1 - 6
A1 - Jie LUO7
A1 - Tingtao CHEN1
A1 - 2
J0 - Journal of Zhejiang University Science B
VL - -1
IS - -1
SP -
EP - 0
%@ 1673-1581
Y1 - 1998
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2500237
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 α-synuclein transgenic mouse model of PD. Specifically, we evaluated its impact on motor function, gut α-synuclein expression, intestinal barrier function, gut microbial composition, and neuropathological changes, with a focus on the PI3K/AKT/GSK-3β signaling pathway. Results: Our findings revealed that C. butyricum-GLP-1 ameliorated motor deficits in PD mice by reducing intestinal α-synuclein accumulation, restoring gut barrier function, and modulating microbial diversity—notably increasing the relative abundance of Prevotella at the genus level. Furthermore, the engineered strain attenuated neuropathological alterations by decreasing phosphorylated α-synuclein (p-α-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-3β 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-3β pathway. These findings provide further theoretical support for the potential application of probiotic-based therapies in Parkinson’s disease treatment.
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