Involvement of RhoA/ROCK Signaling in Aβ-Induced Chemotaxis, Cytotoxicity and Inflammatory Response of Microglial BV2 Cells.

Abstract:

:Reactive microglia clustering around amyloid plaques in brain is a histopathological feature of Alzheimer's disease (AD) and reflects the contribution of neuroinflammation in AD pathogenesis. β-Amyloid peptide (Aβ) has been shown to induce a range of microglial responses including chemotaxis, cytotoxicity and inflammation, but the underlying mechanism is poorly understood. Considering the fundamental role of RhoA/ROCK signaling in cell migration and its broad implication in AD and neuroinflammation, we hypothesized that RhoA/ROCK signaling might be involved in Aβ-induced microglial responses. From in vivo mouse models including APP/PS1 transgene and fibrillar Aβ stereotactic injection, we observed the elevated expression level of RhoA in reactive microglia. Through a series in vitro cell migration, cytotoxicity and biochemistry assays, we found that RhoA/ROCK signaling plays an essential role in Aβ-induced responses of microglial BV2 cells. Small molecular agents Fasudil and Y27632 showed prominent beneficial effects, which implies the therapeutic potential of RhoA/ROCK signaling inhibitors in AD treatment.

journal_name

Cell Mol Neurobiol

authors

Zhang X,Ye P,Wang D,Liu Y,Cao L,Wang Y,Xu Y,Zhu C

doi

10.1007/s10571-019-00668-6

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

637-650

issue

5

eissn

0272-4340

issn

1573-6830

pii

10.1007/s10571-019-00668-6

journal_volume

39

pub_type

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