Amyloid-β peptides induce several chemokine mRNA expressions in the primary microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway
Department of Immunology, Nagoya University Graduate School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya, Aichi 466-8520, Japan. Neuroscience Research
(Impact Factor: 1.94).
12/2006; 56(3):294-9. DOI: 10.1016/j.neures.2006.07.009
Alzheimer's disease (AD) is characterized by the presence of senile plaques composed primarily of amyloid-beta peptide (Abeta) in the brain. Microglia have been reported to surround these Abeta plaques, which have opposite roles, provoking a microglia-mediated inflammatory response that contributes to neuronal cell loss or the removal of Abeta and damaged neurons. To perform these tasks microglia migrate to the sites of Abeta secretion. We herein analyzed the process of chemokine expression induced by Abeta stimulation in primary murine microglia and Ra2 microglial cell line. We found that Abeta1-42 induced the expressions of CCL7, CCL2, CCL3, CCL4 and CXCL2 in the microglia. The signal transduction pathway for the expression of CCL2 and CCL7 mRNA induced by Abeta1-42 was found to depend on phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK), whereas the pathway for CCL4 depended only on PI3K/Akt. These inflammatory chemokine expressions by Abeta stimulation emphasize the contribution of neuroinflammatory mechanisms to the pathogenesis of AD.
Available from: benthamopen.com
- "We have shown that A 25-35 induces Akt and IB phosphorylation within 15 min after addition to culture medium . Further A 1-42 induces Akt and PI3/Akt phosphorylation within 5 min . These results indicate that monomer or soluble oligomer A but not aggregated A bind to cell membrane and induces immflamatory responses. "
The Open Geriatric Medicine Journal 01/2012; 5(1):1-6. DOI:10.2174/1874827901205010001
Available from: Young-Ji Shiao
- "The distribution of microglia is regulated by over-expressing CCL2 or genetically ablation of CCL2 receptor in APP transgenic mice (El Khoury et al., 2007; Yamamoto et al., 2005). Furthermore, mRNA levels of several chemokines in microglia are upregulated by aggregated Ab (Ito et al., 2006). Previous in vitro studies have suggested that the uptake of aggregated Ab by microglia is mediated by scavenger receptors, integrin, and formyl peptide like receptor 1 (FPRL1) (El Khoury et al., 1996; Koenigsknecht and Landreth, 2004; Lorton et al., 2000). "
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ABSTRACT: The number of microglia surrounding senile plaques is correlated with the size of plaques in Alzheimer's disease (AD). It is unclear whether more microglia are passively recruited toward larger senile plaques or, conversely, microglia recruited to senile plaques directly contribute to the growth of plaques. In this study, BV-2 microglia were used to delineate the role of microglia in the growth of plaques using time-lapse recording. Aggregated beta amyloid peptide (Abeta)-induced BV-2 microglia to form clusters. The recruitment of BV-2 microglia bearing membrane-adhered Abeta enlarged preexisting Abeta aggregates. The receptors involved in the microglial uptake of Abeta, including integrin, formyl peptide like receptor 1, and scavenger receptors, also mediated the microglial clustering. Neutralization antibodies against chemokines significantly attenuated Abeta-induced microglial clustering and the enlargement of Abeta aggregates. Our results reveal a novel role of microglia in directly increasing the size of Abeta aggregates and suggest the targeting of Abeta-mediated microglial chemotactic migration in developing therapeutic interventions for AD.
Neuroscience Research 05/2009; 63(4):280-7. DOI:10.1016/j.neures.2009.01.001 · 1.94 Impact Factor
Available from: Jae-Kyung Lee
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ABSTRACT: During the last two decades, a wealth of animal and human studies has implicated inflammation-derived oxidative stress and
cytokine-dependent neurotoxicity in the progressive degeneration of the dopaminergic nigrostriatal pathway, the hallmark of
Parkinson’s disease (PD). In this review, we discuss the various hypotheses regarding the role of microglia and other immune
cells in PD pathogenesis and progression, the inflammatory mechanisms implicated in disease progression from pre-clinical
and clinical studies, the recent evidence that systemic inflammation can trigger microglia activation in PD-relevant central
nervous system regions, the synergism between gene products linked to parkinsonian phenotypes (α-synuclein, parkin, Nurr1,
and regulator of G-protein signaling-10) and neuroinflammation in promoting neurodegeneration of the nigrostriatal pathway,
and the latest update on meta-analysis of epidemiological studies on the risk-lowering effects of anti-inflammatory drug regimens.
Journal of Neuroimmune Pharmacology 12/2009; 4(4):419-429. DOI:10.1007/s11481-009-9176-0 · 4.11 Impact Factor
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