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CD44 deficiency represses neuroinflammation and rescues dopaminergic neurons in a mouse model of Parkinson's disease.

Yuejun Wang | Li Li | Yuting Wu | Shouping Zhang | Qianqian Ju | Yinuo Yang | Yan Jin | Hui Shi | Cheng Sun
Pharmacological research | 2022

CD44 is a transmembrane protein that transduces extracellular stimuli to immune response. Neuroinflammation is a causative factor in neurodegenerative diseases, such as Parkinson's disease (PD). Owing to its role in inflammation, this study investigated whether CD44 is involved in the pathological progression of PD. Our data showed that CD44 deficiency largely abolished proinflammatory cytokine expression in primary microglia and astrocytes. In PD model mice, CD44 knockout improved behavioral defects, prevented TH loss in the SNpc and striatum, and blocked activation of microglia and astrocytes. Moreover, CD44 neutralization by anti-CD44 antibody recapitulated the phenotypes observed in CD44 knockout mice. Mechanistically, CD44 neutralization blocked TLR4 expression and NF-κB p65 nuclear translocation induced by lipopolysaccharide in BV2 cells. Overall, our results indicate that CD44 deficiency has a beneficial role against PD, which is likely due to repression of the TLR4/NF-κB axis, leading to reduced neuroinflammation. Therefore, CD44 might be a therapeutic target for the development of anti-PD agents.

Pubmed ID: 35182746

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This is a list of tools and resources that we have found mentioned in this publication.


Molecular Probes (tool)

RRID:SCR_013318

An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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CD44 (antibody)

RRID:AB_2885107

This unknown targets CD44

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Anti Iba1, Rabbit (antibody)

RRID:AB_839506

This polyclonal targets Iba-1

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Tyrosine Hydroxylase antibody - Neuronal Marker (antibody)

RRID:AB_2240393

This polyclonal targets Tyrosine Hydroxylase - Neuronal Marker

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InVivoMab polyclonal rat IgG (antibody)

RRID:AB_1107795

This isotype control targets Unknown Specificity

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Hoechst 33342 (antibody)

RRID:AB_10626776

This unknown targets Hoechst 33342

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TLR4 antibody [76B357.1] (antibody)

RRID:AB_446735

This monoclonal targets TLR4

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Phospho-NF-κB p65 (Ser536) (93H1) Rabbit mAb (antibody)

RRID:AB_331284

This monoclonal targets NF-KappaB p65, phospho (Ser536)

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STOCK Cd44tm1Hbg/J (organism)

RRID:IMSR_JAX:003899

Mus musculus with name STOCK Cd44tm1Hbg/J from IMSR.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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