Secreted Forms of the Amyloid-β Precursor Protein Are Ligands for the Class A Scavenger Receptor

Santiago‐García, Juan; Mas‐Oliva, Jaime; Innerarity, Thomas L.; Pitas, Robert E.

doi:10.1074/jbc.m102879200

Cited by 48 publications

(28 citation statements)

References 55 publications

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“…It is also possible that the immunostaining in gray matter could be the result of -sAPP uptake by glial cells, for instance during a scavenging process. sAPP has been shown to bind to the scavenger receptor and to be internalised in transfected CHO cells [27]. High expression levels of the scavenging receptor have been detected near amyloid plaques in AD brain.…”

Section: Discussionmentioning

confidence: 99%

β‐secretase‐cleaved amyloid precursor protein in Alzheimer brain: a morphologic study

Sennvik

Bogdanović

Volkmann

et al. 2004

J Cellular Molecular Medi

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Alzheimer's disease (AD) is characterised by the presence of intracellular neurofibrillary tangles (NFTs), neurofibrillary threads, extracellular amyloid plaques and accumulation of amyloid in cerebral blood vessels. The major component of the amyloid is a 39-43 amino acids peptide calledamyloid (A ). A derives from the amyloid precursor protein (APP), which is a widely expressed transmembrane protein [1]. Although the function of APP is not known, it has been proposed to have a role in regulation of neurite extension, synapse formation, neuronal development and neuroprotection [2][3][4].A is produced from APP via proteolytic cleavage by proteases called -and -secretase. Abstract-amyloid (A ) is the main constituent of senile plaques seen in Alzheimer's disease. A is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases -and -secretase. In this study, we examined content and localization of -secretase-cleaved APP ( -sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular -sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. -sAPP was found to be localized in astrocytes and in axons. We found the -sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal -sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. -sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered -sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP.

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Section: Discussionmentioning

confidence: 99%

β‐secretase‐cleaved amyloid precursor protein in Alzheimer brain: a morphologic study

Sennvik

Bogdanović

Volkmann

et al. 2004

J Cellular Molecular Medi

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“…The The low-affinity APP-induced TGF␤2-specific receptor is APP. To address whether the TGF␤2-specific receptor is APP itself or other unidentified proteins whose expression are induced by APP, we performed competition experiments by adding as a competitor larger amounts of soluble APP␣ of human APP695 (sAPP), corresponding to amino acids 1 to 612 of APP695 (the numbering follows that of Kang et al and Santiago-Garcia et al [17,41]), to binding assays (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

Transforming Growth Factor β2 Is a Neuronal Death-Inducing Ligand for Amyloid-β Precursor Protein

Hashimoto¹,

Chiba²,

Yamada

et al. 2005

Molecular and Cellular Biology

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APP, amyloid ␤ precursor protein, is linked to the onset of Alzheimer's disease (AD). We have here found that transforming growth factor ␤2 (TGF␤2), but not TGF␤1, binds to APP. The binding affinity of TGF␤2 to APP is lower than the binding affinity of TGF␤2 to the TGF␤ receptor. On binding to APP, TGF␤2 activates an APP-mediated death pathway via heterotrimeric G protein G o , c-Jun N-terminal kinase, NADPH oxidase, and caspase 3 and/or related caspases. Overall degrees of TGF␤2-induced death are larger in cells expressing a familial AD-related mutant APP than in those expressing wild-type APP. Consequently, superphysiological concentrations of TGF␤2 induce neuronal death in primary cortical neurons, whose one allele of the APP gene is knocked in with the V642I mutation. Combined with the finding indicated by several earlier reports that both neural and glial expression of TGF␤2 was upregulated in AD brains, it is speculated that TGF␤2 may contribute to the development of AD-related neuronal cell death.

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“…The SR-A binds and internalizes microaggregates of the 42-amino acid form of A␤ in vitro (9). In addition, we recently reported that the SR-A binds secreted forms of APP (8). The A␤ peptide and secreted APP are major constituents of senile plaques and cerebrovascular deposits in patients with AD and Down's syndrome (31)(32)(33).…”

Section: Sr-a Mediates Macrophage Adhesion To the Extracellular Matrimentioning

confidence: 99%

“…In addition, the SR-A binds a limited number of native proteins. We recently showed that the ␣-secretase cleavage products of the three main isoforms of the amyloid precursor protein (APP695, APP751, and APP770) are ligands for the SR-A (8). The SR-A also binds the amyloid-␤ (A␤) peptide (9), another enzymatic cleavage product of APP and a major component of senile plaques in Alzheimer's disease (AD).…”

mentioning

confidence: 99%

The Class A Scavenger Receptor Binds to Proteoglycans and Mediates Adhesion of Macrophages to the Extracellular Matrix

Santiago‐García¹,

Kodama²,

Pitas³

2003

Journal of Biological Chemistry

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Secreted Forms of the Amyloid-β Precursor Protein Are Ligands for the Class A Scavenger Receptor

Cited by 48 publications

References 55 publications

β‐secretase‐cleaved amyloid precursor protein in Alzheimer brain: a morphologic study

β‐secretase‐cleaved amyloid precursor protein in Alzheimer brain: a morphologic study

Transforming Growth Factor β2 Is a Neuronal Death-Inducing Ligand for Amyloid-β Precursor Protein

The Class A Scavenger Receptor Binds to Proteoglycans and Mediates Adhesion of Macrophages to the Extracellular Matrix

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