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CXCR4/CXCR7-SDF1 Axis-Based Targeting Treatment of Huntington’s Disease with Blood-Brain Barrier Permeable Neural Stem Cell-Derived Nanovesicles Reinforced by Biomimetic Nanozymes

ABSTRACT: Commencing with the production of toxic mutant huntingtin protein, many pathogenic factors, including mitochondrial dysfunction, overproduced reactive oxygen species (ROS) and neuroinflammation interactively accelerate the progression of Huntington’s disease (HD), causing the dysfunction and death of neurons, especially striatal medium spiny neurons. In light of that, we developed versatile neural stem cells (NSCs)-derived nanovesicles incorporating ultrasmall citrate modified-manganese oxide nanoparticles (CMnNZs) as well as pre-stimulating with IFNγ (MnINNVs). CMnNZs and IFNγ markedly increased the level of therapeutic factors in MnINNVs. Furthermore, MnINNVs are able to bypass the blood-brain barrier and target the inflammatory sites of HD through the SDF1-CXCR4/CXCR7 axis. After being uptake by neurons, microglia, and astrocytes, MnINNVs alleviate HD-like mice phenotype by scavenging ROS, promoting the conversion of microglia and astrocytes phenotypes to reduce neuroinflammation, and further rescuing neurons. Our study not only offers a novel therapy for HD but also presents new strategies to enhance the wholesome effects of NSCs-based therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE284688 | GEO | 2025/12/19

REPOSITORIES: GEO

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CXCR4/CXCR7-SDF1 Axis-Based Targeting Treatment of Huntington’s Disease with Blood-Brain Barrier Permeable Neural Stem Cell-Derived Nanovesicles Reinforced by Biomimetic Nanozymes

Project description:Commencing with the production of toxic mutant huntingtin protein, many pathogenic factors, including mitochondrial dysfunction, overproduced reactive oxygen species (ROS) and neuroinflammation interactively accelerate the progression of Huntington’s disease (HD), causing the dysfunction and death of neurons, especially striatal medium spiny neurons. In light of that, we developed versatile neural stem cells (NSCs)-derived nanovesicles incorporating ultrasmall citrate modified-manganese oxide nanoparticles (CMnNZs) as well as pre-stimulating with IFNγ (MnINNVs). CMnNZs and IFNγ markedly increased the level of therapeutic factors in MnINNVs. Furthermore, MnINNVs are able to bypass the blood-brain barrier and target the inflammatory sites of HD through the SDF1-CXCR4/CXCR7 axis. After being uptake by neurons, microglia, and astrocytes, MnINNVs alleviate HD-like mice phenotype by scavenging ROS, promoting the conversion of microglia and astrocytes phenotypes to reduce neuroinflammation, and further rescuing neurons. Our study not only offers a novel therapy for HD but also presents new strategies to enhance the wholesome effects of NSCs-based therapies.

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CXCR4/CXCR7-SDF1 Axis-Based Targeting Treatment of Huntington’s Disease with Blood-Brain Barrier Permeable Neural Stem Cell-Derived Nanovesicles Reinforced by Biomimetic Nanozymes

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