MEGF10 functions as a receptor for the uptake of amyloid‐β

Singh, Thoudam Debraj; Park, Seung Yoon; Bae, Jung Hoon; Yun, Youngeun; Bae, Yong Chul; Park, Rang Woon; Kim, In San

doi:10.1016/j.febslet.2010.08.050

Cited by 42 publications

(33 citation statements)

References 36 publications

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“…Nevertheless, little is known about the CTXN3 protein (described for the first time in 2007): it has a single membrane-spanning domain and appears to be expressed only in the kidney and in the brain. 46 Another interesting gene of this locus, MEGF10, encodes a phagocytic receptor that could have a role in Aβ 1–42 uptake in the brain 47 and a suggestive association with cognitive decline in AD patients has been recently reported within this gene. 48 …”

Section: Discussionmentioning

confidence: 99%

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

et al. 2014

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Amyloid beta (Aβ) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aβ peptides’ functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aβ peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aβ-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aβ1–40 and Aβ1–42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10−5). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aβ1–42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aβ1–42 secretion. In conclusion, our study results suggest that plasma Aβ peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.

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Section: Discussionmentioning

confidence: 99%

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

et al. 2014

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“…In addition, reduction of cellular cholesterol and sphingolipid levels decrease Ab uptake [114]. More directly, treatment of lipid raft-dependent endocytosis inhibitor or inhibition of clathrin-dependent endocytosis decreases Ab uptake [47,115,116]. Collectively, such direct interaction with lipid rafts and clathrinmediated endocytosis may provide way(s) for Ab uptake.…”

Section: Receptors For Ab Internalizationmentioning

confidence: 99%

Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer’s disease

Kam

Gwon

Jung

2014

Cell. Mol. Life Sci.

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Alzheimer's disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-β (Aβ) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative Aβ-binding receptors that mediate Aβ neurotoxicity in cells and models of AD. Once Aβ interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, Aβ can also be internalized into neurons through unidentified Aβ receptors and induces malfunction of subcellular organelles, which explains some part of Aβ neurotoxicity. Understanding the neurotoxic signaling initiated by Aβ-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on Aβ-binding receptors and the neurotoxicity of oligomeric Aβ.

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“…The authors further showed that reduction of cellular cholesterol and sphingolipid levels significantly decreased A β uptake [65]. A recent study by Singh et al [66] using mouse neuroblastomas also found colocalization of internalized A β with CTxB. The authors pharmacologically inhibited lipid raft-dependent endocytosis which resulted in decreased uptake of soluble A β [66].…”

Section: Aβ Binding Aggregation and Internalization At Lipid Raftsmentioning

confidence: 99%

“…A recent study by Singh et al [66] using mouse neuroblastomas also found colocalization of internalized A β with CTxB. The authors pharmacologically inhibited lipid raft-dependent endocytosis which resulted in decreased uptake of soluble A β [66]. Thus far it is unclear whether the lipid components or the associated receptor proteins are responsible for initiating A β uptake at lipid rafts.…”

Section: Aβ Binding Aggregation and Internalization At Lipid Raftsmentioning

confidence: 99%

Mechanisms of Amyloid‐Beta Peptide Uptake by Neurons: The Role of Lipid Rafts and Lipid Raft‐Associated Proteins

Lai

McLaurin

2010

International Journal of Alzheimer's Disease

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A hallmark pathological feature of Alzheimer's disease (AD) is the accumulation of extracellular plaques composed of the amyloid-beta (Aβ) peptide. Thus, classically experiments were designed to examine Aβ toxicities within the central nervous system (CNS) from the extracellular space. However, a significant amount of evidence now suggests that intraneuronal accumulation of Aβ is neurotoxic and may play an important role in the disease progression of AD. One of the means by which neurons accumulate intracellular Aβ is through uptake of extracellular Aβ peptides, and this process may be a potential link between Aβ generation, synaptic dysfunction, and AD pathology. Recent studies have found that neuronal internalization of Aβ involves lipid rafts and various lipid raft-associated receptor proteins. Uptake mechanisms independent of lipid rafts have also been implicated. The aim of this paper is to summarize these findings and discuss their significance in the pathogenesis of AD.

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MEGF10 functions as a receptor for the uptake of amyloid‐β

Cited by 42 publications

References 36 publications

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

A genome-wide association meta-analysis of plasma Aβ peptides concentrations in the elderly

Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer’s disease

Mechanisms of Amyloid‐Beta Peptide Uptake by Neurons: The Role of Lipid Rafts and Lipid Raft‐Associated Proteins

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