The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway

Journal of Neuroinflammation
Yinquan FangHong Liao

Abstract

Alzheimer's disease is characterized by progressive accumulation of β-amyloid (Aβ)-containing amyloid plaques, and microglia play a critical role in internalization and degradation of Aβ. Our previous research confirmed that Nogo-66 binding to Nogo receptors (NgR) expressed on microglia inhibits cell adhesion and migration in vitro. The adhesion and migration of microglia isolated from WT and APP/PS1 mice from different ages were measured by adhesion assays and transwells. After NEP1-40 (a competitive antagonist of Nogo/NgR pathway) was intracerebroventricularly administered via mini-osmotic pumps for 2 months in APP/PS1 transgenic mice, microglial recruitment toward Aβ deposits and CD36 expression were determined. In this paper, we found that aging led to a reduction of microglia adhesion and migration to fAβ1-42 in WT and APP/PS1 mice. The adhesion and migration of microglia to fAβ1-42 were downregulated by the Nogo, which was mediated by NgR, and the increased inhibitory effects of the Nogo could be observed in aged mice. Moreover, Rho GTPases contributed to the effects of the Nogo on adhesion and migration of microglia to fAβ1-42 by regulating cytoskeleton arrangement. Furthermore, blocking the Nogo/NgR pathway enhanced rec...Continue Reading

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Citations

Nov 20, 2020·Neuroscience·Ana-Maria DobriMihail Eugen Hinescu
May 15, 2020·Neurobiology of Aging·Chunxu YuanHong Qing
Jan 11, 2022·Molecular Neurobiology·Juan R PereaJesús Avila

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Methods Mentioned

BETA
GTPases
protein assay
Assay
fluorescence microscopy
GTPase

Software Mentioned

Pro Plus
GraphPad
Image
GraphPad Prism
Quantity One

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