Abstract
Microglia plays a critical role in the brain aging process and in Alzheimer's disease (AD). It has been reported the ability of microglia to clear Aβ decreases with age and progression of AD pathology. Nogo-A/NgR signaling pathway not only arreste neurite outgrowth but also involve AD pathology. NgR expressed on the neuron also expresses on the microglia and Nogo-A/NgR signaling pathway mediates neuroinflammation via modulating microglia adhesion and migration. Therefore i n the present study we would like explore the role of Nogo-A/NgR signaling pathway on microglia adhesion and migration to A β deposition during aging in vitro. Adhesion assay, Boyden chamber migration assay and Western blot analysis were used for determinating ability of migration and adhesion of microglia isolated from different age to A β fibrils in vitro. Our results show that microglia from aging mice decreased the adhesion and migration to A β fibrils compared with microglia from young mice in vitro. Nogo-A inhibited their adhesion and migration to Aβ fibrils in vitro, which were mediated by NgR. We also found RhoA as the downstream signal transducers involved in the microglia adhesion and migration to A β fibrils in the presence of Nogo-A. Nogo-A also inhibited microglia polarization and membrane protrusion formation, thus might eventually contribute to the decreasing of microglia adhesion and migration to A β fibrils. Our data indicate that Nogo-A inhibits adhesion and migration of microglia to A β fibrils in the aging via NgR and Rho pathway. The Nogo-A/NgR pathway will maybe provide a potential target for modifying the course of AD and highlights the role of brain inflammation in the AD disease.
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More From: Alzheimer's & Dementia: The Journal of the Alzheimer's Association
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