β1-integrin-dependent migration of microglia in response to neuron-released α-synuclein.

β1-integrin-dependent migration of microglia in response to neuron-released α-synuclein. Exp Mol Med. 2014;46:e91 Authors: Kim C, Cho ED, Kim HK, You S, Lee HJ, Hwang D, Lee SJ Abstract Chronic neuroinflammation is an integral pathological feature of major neurodegenerative diseases. The recruitment of microglia to affected brain regions and the activation of these cells are the major events leading to disease-associated neuroinflammation. In a previous study, we showed that neuron-released α-synuclein can activate microglia through activating the Toll-like receptor 2 (TLR2) pathway, resulting in proinflammatory responses. However, it is not clear whether other signaling pathways are involved in the migration and activation of microglia in response to neuron-released α-synuclein. In the current study, we demonstrated that TLR2 activation is not sufficient for all of the changes manifested by microglia in response to neuron-released α-synuclein. Specifically, the migration of and morphological changes in microglia, triggered by neuron-released α-synuclein, did not require the activation of TLR2, whereas increased proliferation and production of cytokines were strictly under the control of TLR2. Construction of a hypothetical signaling network using computational tools and experimental validation with various peptide inhibitors showed that β1-integrin was necessary for both the morphological changes and the migration. However, n...
Source: exp Mol Med - Category: Molecular Biology Authors: Tags: Exp Mol Med Source Type: research