Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils

Khoury, Joseph El; Hickman, SE; Thomas, Christian A.; Cao, Long; Silverstein, Samuel C.; Loike, John D.

doi:10.1038/382716a0

Cited by 724 publications

(557 citation statements)

References 18 publications

Supporting

Mentioning

539

Contrasting

Unclassified

Order By: Relevance

“…3 C and D, respectively). As MSR has been proposed as a microglial receptor for A␤ (41) and is also expressed at increased levels in AD (42), this suggests a mechanism whereby neuronal stimulation of RAGE could enhance subsequent microglial-A␤ interaction. M-CSF also enhanced BV-2 cell expression of apoE, as shown by the increased level of antigen (Fig.…”

Section: Resultsmentioning

confidence: 99%

Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease

Yan

Zhu²,

Fu³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

387

153

View full text Add to dashboard Cite

In Alzheimer disease (AD), neurons are thought to be subjected to the deleterious cytotoxic effects of activated microglia. We demonstrate that binding of amyloidbeta peptide (A␤) to neuronal Receptor for Advanced Glycation Endproduct (RAGE), a cell surface receptor for A␤, induces macrophage-colony stimulating factor (M-CSF) by an oxidant sensitive, nuclear factor B-dependent pathway. AD brain shows increased neuronal expression of M-CSF in proximity to A␤ deposits, and in cerebrospinal fluid from AD patients there was Ϸ5-fold increased M-CSF antigen (P < 0.01), compared with age-matched controls. M-CSF released by A␤-stimulated neurons interacts with its cognate receptor, c-fms, on microglia, thereby triggering chemotaxis, cell proliferation, increased expression of the macrophage scavenger receptor and apolipoprotein E, and enhanced survival of microglia exposed to A␤, consistent with pathologic findings in AD. These data delineate an inflammatory pathway triggered by engagement of A␤ on neuronal RAGE. We suggest that M-CSF, thus generated, contributes to the pathogenesis of AD, and that M-CSF in cerebrospinal fluid might provide a means for monitoring neuronal perturbation at an early stage in AD.

show abstract

Section: Resultsmentioning

confidence: 99%

Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease

Yan

Zhu²,

Fu³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

387

153

View full text Add to dashboard Cite

show abstract

“…Consistent with a mechanism involving membrane receptors, we have shown that the lectin ConA, which forms clusters of membrane glycoproteins on the cell surface, also causes neurodegeneration and apoptotic death in cultured neurons similar to that observed with A␤ while succinyl ConA, which binds but does not cross-link, is inactive (39). Recently, Burdick,et al (40) have shown that a substantial portion of the A␤ that binds to cells can be removed by treatment with trypsin and several receptors that appear to bind A␤ peptides have been identifed (41)(42)(43)(44)(45)(46). In the case of the receptor for advanced glycation end products (RAGE), some evidence has been presented that it may be directly involved in A␤-induced neurotoxicity (45).…”

Section: Discussionmentioning

confidence: 99%

All-D-Enantiomers of β-Amyloid Exhibit Similar Biological Properties to All-L-β-Amyloids

Cribbs

Pike²,

Weinstein³

et al. 1997

Journal of Biological Chemistry

View full text Add to dashboard Cite

The amyloidogenic peptide ␤-amyloid has previously been shown to bind to neurons in the form of fibrillar clusters on the cell surface, which induces neurodegeneration and activates a program of cell death characteristic of apoptosis. To further investigate the mechanism of A␤ neurotoxicity, we synthesized the all-D-and all-Lstereoisomers of the neurotoxic truncated form of A␤ (A␤ [25][26][27][28][29][30][31][32][33][34][35] ) and the full-length peptide (A␤ 1-42 ) and compared their physical and biological properties. We report that the purified peptides exhibit nearly identical structural and assembly characteristics as assessed by high performance liquid chromatography, electron microscopy, circular dichroism, and sedimentation analysis. In addition, both enantiomers induce similar levels of toxicity in cultured hippocampal neurons. These data suggest that the neurotoxic actions of A␤ result not from stereoisomer-specific ligand-receptor interactions but rather from A␤ cellular interactions in which fibril features of the amyloidogenic peptide are a critical feature. The promiscuous nature of these ␤-sheet-containing fibrils suggests that the accumulation of amyloidogenic peptides in vivo as extracellular deposits represents a site of bioactive peptides with the ability to provide inappropriate signals to cells leading to cellular degeneration and disease.Alzheimer's disease (AD), 1 vascular dementia, and hereditary cerebral hemorrhage with the Dutch type are diseases that share an invariant pathological feature, the accumulation of an amyloidogenic peptide into insoluble fibrillar extracellular deposits. In all three cases, the major component of the extracellular debris is the ␤-amyloid peptide (A␤) that is derived from the proteolytic processing of the large membraneanchored amyloid precursor protein (APP) encoded by a single gene located on chromosome 21 (1). However, the biological significance of these amyloid deposits has been extensively debated as to whether they are a causative factor of each disease or merely a metabolically inert end product lacking in biological activity. Evidence in support of a causative role for A␤ in neuropathology comes from genetic analysis of the APP gene where several autosomal dominant mutations have been linked with AD and hereditary cerebral hemorrhage with the Dutch type (2, 3). In a recent in vitro study, the ␤-APP 717 mutation consistently caused a significant increase in the percentage of the longer and more amyloidogenic A␤ 1-42 over the shorter A␤ 1-40 (4). Incorporation of this same mutation into a transgenic mouse model yields A␤ deposition and neuropathology that closely parallels that observed in AD (5). Additional in vivo evidence suggesting that the A␤ peptide itself may be biologically active comes from a transgenic model overexpressing A␤ , in which A␤ transgene expression was detected in a variety of peripheral tissues but histopathological changes were restricted to the brain. Moreover, the neurodegeneration was largely limited to the cerebral cortex, ...

show abstract

“…Brain and microglial up-regulation of PRRs members has been observed in human and experimental AD ( [3,67,21,258]). The Ab peptide was shown to activate microglia cells through the interaction with specific PRR: (a) scavenger receptors, including scavenger receptor class-A (SR-A), SR-B1 and CD36, that mediate Ab endocytosis and induce ROS production ( [46,66]); (b) macrophage receptor with collagenous domain (MARCO), a scavenger receptor that mediates adhesion of Ab to microglia and the cytoskeleton rearrangements induced by this peptide [84]; (c) the receptor for advanced glycation endproducts (RAGE), a member of the immunoglobulin superfamily, responsible for the induction of the inflammatory response stimulated by Ab ( [6,143,258]). …”

Section: Animal Models Of Alzheimer's Diseasementioning

confidence: 99%

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Vegeto

Benedusi

Maggi

2008

Frontiers in Neuroendocrinology

278

206

View full text Add to dashboard Cite

a b s t r a c tRecent studies highlight the prominent role played by estrogens in protecting the central nervous system (CNS) against the noxious consequences of a chronic inflammatory reaction. The neurodegenerative process of several CNS diseases, including Multiple Sclerosis, Alzheimer's and Parkinson's Diseases, is associated with the activation of microglia cells, which drive the resident inflammatory response. Chronically stimulated during neurodegeneration, microglia cells are thought to provide detrimental effects on surrounding neurons. The inhibitory activity of estrogens on neuroinflammation and specifically on microglia might thus be considered as a beneficial therapeutic opportunity for delaying the onset or progression of neurodegenerative diseases; in addition, understanding the peculiar activity of this female hormone on inflammatory signalling pathways will possibly lead to the development of selected anti-inflammatory molecules. This review summarises the evidence for the involvement of microglia in neuroinflammation and the anti-inflammatory activity played by estrogens specifically in microglia.

show abstract

Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils

Cited by 724 publications

References 18 publications

Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease

Amyloid-β peptide–Receptor for Advanced Glycation Endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: A proinflammatory pathway in Alzheimer disease

All-D-Enantiomers of β-Amyloid Exhibit Similar Biological Properties to All-L-β-Amyloids

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

Contact Info

Product

Resources

About