Galectin 3–binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein

Seki, Tsuneyoshi; Kanagawa, Motoi; Kobayashi, Kenzo; Kowa, Hisatomo; Yahata, Naoki; Maruyama, Kei; Iwata, Nobuhisa; Inoue, Haruhisa; Toda, Tatsushi

doi:10.1074/jbc.ra119.008703

Cited by 33 publications

(19 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protein Gal-3BP is associated with the immune system [94], as it functions as a suppressor of inflammatory responses by blocking the NF-kB signalling pathway. Remarkably, Gal-3BP can suppress Aβ production through inhibition of the amyloid precursor protein (APP) processing by β-secretase [95]. Thus, the delivery of Gal-3BP into neurons and microglia in the brain through IN administration of EVs might be beneficial for restraining neuroinflammation and reducing amyloid-beta (Aβ) plaques in AD.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

Upadhya

Madhu

Attaluri

et al. 2020

J of Extracellular Vesicle

127

145

View full text Add to dashboard Cite

Grafting of neural stem cells (NSCs) derived from human induced pluripotent stem cells (hiPSCs) has shown promise for brain repair after injury or disease, but safety issues have hindered their clinical application. Employing nano-sized extracellular vesicles (EVs) derived from hiPSC-NSCs appears to be a safer alternative because they likely have similar neuroreparative properties as NSCs and are amenable for non-invasive administration as an autologous or allogeneic off-theshelf product. However, reliable methods for isolation, characterization and testing the biological properties of EVs are critically needed for translation. We investigated signatures of miRNAs and proteins and the biological activity of EVs, isolated from hiPSC-NSCs through a combination of anion-exchange chromatography (AEC) and size-exclusion chromatography (SEC). AEC and SEC facilitated the isolation of EVs with intact ultrastructure and expressing CD9, CD63, CD81, ALIX and TSG 101. Small RNA sequencing, proteomic analysis, pathway analysis and validation of select miRNAs and proteins revealed that EVs were enriched with miRNAs and proteins involved in neuroprotective, anti-apoptotic, antioxidant, anti-inflammatory, blood-brain barrier repairing, neurogenic and Aβ reducing activities. Besides, EVs comprised miRNAs and/or proteins capable of promoting synaptogenesis, synaptic plasticity and better cognitive function. Investigations using an in vitro macrophage assay and a mouse model of status epilepticus confirmed the antiinflammatory activity of EVs. Furthermore, the intranasal administration of EVs resulted in the incorporation of EVs by neurons, microglia and astrocytes in virtually all adult rat and mouse brain regions, and enhancement of hippocampal neurogenesis. Thus, biologically active EVs containing miRNAs and proteins relevant to brain repair could be isolated from hiPSC-NSC cultures, making them a suitable biologic for treating neurodegenerative disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

Upadhya

Madhu

Attaluri

et al. 2020

J of Extracellular Vesicle

127

145

View full text Add to dashboard Cite

show abstract

“…Galectin-3-binding protein (G3BP) was just recently shown to inhibit the processing of APP into Aβ by direct interaction with APP [ 299 ]. Co-deposition of G3BP in senile plaque may be a consequence of this interaction but it could also result in reduced inhibitory capacity and thereby a positive feedback loop for Aβ production.…”

Section: Survey Of Extracellular Proteins That Associate With Aβmentioning

confidence: 99%

Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology

Rahman

Lendel

2021

Mol Neurodegeneration

125

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is pathologically defined by the presence of fibrillar amyloid β (Aβ) peptide in extracellular senile plaques and tau filaments in intracellular neurofibrillary tangles. Extensive research has focused on understanding the assembly mechanisms and neurotoxic effects of Aβ during the last decades but still we only have a brief understanding of the disease associated biological processes. This review highlights the many other constituents that, beside Aβ, are accumulated in the plaques, with the focus on extracellular proteins. All living organisms rely on a delicate network of protein functionality. Deposition of significant amounts of certain proteins in insoluble inclusions will unquestionably lead to disturbances in the network, which may contribute to AD and copathology. This paper provide a comprehensive overview of extracellular proteins that have been shown to interact with Aβ and a discussion of their potential roles in AD pathology. Methods that can expand the knowledge about how the proteins are incorporated in plaques are described. Top-down methods to analyze post-mortem tissue and bottom-up approaches with the potential to provide molecular insights on the organization of plaque-like particles are compared. Finally, a network analysis of Aβ-interacting partners with enriched functional and structural key words is presented.

show abstract

“…GPLD1 gene has been reported to interact with Apolipoprotein A1 and APOA4 (Deeg et al, 2001) and Lin et al, 2015 have shown that the low levels of APOA1 , APOC3 , and APOA4 are associated with risk of AD. Importantly, the GPLD1 is a candidate gene that modulates Aβ production (Seki et al, 2020). Wilmsdorff et al, (2013) reported that the increased SLC1A3 expression indicates facilitated transport and may result in reduced glutamate neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

Novel DNA methylation marker discovery by assumption‐free genome‐wide association analysis of cognitive function in twins

et al. 2021

View full text Add to dashboard Cite

Privileged by rapid increase in available epigenomic data, epigenome‐wide association studies (EWAS) are to make a profound contribution to understand the molecular mechanism of DNA methylation in cognitive aging. Current statistical methods used in EWAS are dominated by models based on multiple assumptions, for example, linear relationship between molecular profiles and phenotype, normal distribution for the methylation data and phenotype. In this study, we applied an assumption‐free method, the generalized correlation coefficient (GCC), and compare it to linear models, namely the linear mixed model and kinship model. We use DNA methylation associated with a cognitive score in 400 and 206 twins as discovery and replication samples respectively. DNA methylation associated with cognitive function using GCC, linear mixed model, and kinship model, identified 65 CpGs (p < 1e‐04) from discovery sample displaying both nonlinear and linear correlations. Replication analysis successfully replicated 9 of these top CpGs. When combining results of GCC and linear models to cover diverse patterns of relationships, we identified genes like KLHDC4, PAPSS2, and MRPS18B as well as pathways including focal adhesion, axon guidance, and some neurological signaling. Genomic region‐based analysis found 15 methylated regions harboring 11 genes, with three verified in gene expression analysis, also the 11 genes were related to top functional clusters including neurohypophyseal hormone and maternal aggressive behaviors. The GCC approach detects valuable methylation sites missed by traditional linear models. A combination of methylation markers from GCC and linear models enriched biological pathways sensible in neurological function that could implicate cognitive performance and cognitive aging.

show abstract

Galectin 3–binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein

Cited by 33 publications

References 47 publications

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

Extracellular vesicles from human iPSC‐derived neural stem cells: miRNA and protein signatures, and anti‐inflammatory and neurogenic properties

Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology

Novel DNA methylation marker discovery by assumption‐free genome‐wide association analysis of cognitive function in twins

Contact Info

Product

Resources

About