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Src Inhibition Attenuates Neuroinflammation and Protects Dopaminergic Neurons in Parkinson's Disease Models.

Frontiers in neuroscience (2020-03-07)
Hanyu Yang, Lu Wang, Caixia Zang, Yue Wang, Junmei Shang, Zihong Zhang, Hui Liu, Xiuqi Bao, Xiaoliang Wang, Dan Zhang
ABSTRACT

Chronic neuroinflammation is of great importance in the pathogenesis of Parkinson's disease (PD). During the process of neuroinflammation, overactivated microglia release many proinflammatory factors, which eventually induce neurodegeneration. Inhibition of excessive microglial activation is regarded as a promising strategy for PD treatment. Src is a non-receptor tyrosine kinase that is closely related to tumors. Recently, some reports indicated that Src is a central mediator in multiple signaling pathways including neuroinflammation. The aim of our study was to demonstrate the role of Src in microglial regulation and neuroinflammation. The lipopolysaccharide (LPS)-stimulated BV2 microglia model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model were applied in this study. The results showed that inhibition of Src could significantly relieve microgliosis and decrease levels of inflammatory factors. Besides, inhibition of Src function reduced the loss of dopaminergic neurons and improved the motor behavior of the MPTP-treated mice. Thus, this study not only verified the critical role of Src tyrosine kinase in neuroinflammation but also further proved that interfering neuroinflammation is beneficial for PD treatment. More importantly, this study shed a light on the hypothesis that Src tyrosine kinase might be a potential therapeutic target for PD and other neuroinflammation-related diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Millipore
Immobilon-P PVDF Membrane, 1 roll, 26.5 cm x 3.75 m, 0.45 µm pore size, Hydrophobic PVDF Transfer Membrane for western blotting.
Sigma-Aldrich
Poly-L-lysine hydrobromide, mol wt 150,000-300,000
Sigma-Aldrich
Carboxymethylcellulose sodium salt, Medium viscosity
Sigma-Aldrich
PP2, ≥98% (HPLC)