A5061190366- Glycosylation and Glycoproteins Research
- Alzheimer's disease research and treatments
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Advanced Glycation End Products research
- Drug Transport and Resistance Mechanisms
- Intracerebral and Subarachnoid Hemorrhage Research
- Polyamine Metabolism and Applications
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Biological Research and Disease Studies
- Protein Tyrosine Phosphatases
- Proteoglycans and glycosaminoglycans research
- Asthma and respiratory diseases
- Liver physiology and pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Neonatal Respiratory Health Research
- Immune Response and Inflammation
- Click Chemistry and Applications
- Cellular transport and secretion
- Supramolecular Self-Assembly in Materials
- Lysosomal Storage Disorders Research
- Amino Acid Enzymes and Metabolism
- Dementia and Cognitive Impairment Research
Fukushima Medical University
2018-2024
RIKEN
2012-2023
Joint Research Center
2013-2019
RIKEN Center for Sustainable Resource Science
2016
Wacom (Japan)
2015
Innovation Cluster (Canada)
2013-2014
RIKEN Advanced Science Institute
2008-2013
Max Planck Society
2013
Japan Science and Technology Agency
2004-2009
Gunma University
2009
The deposition of amyloid β-peptide (Aβ) in the brain is closely associated with development Alzheimer's disease. Aβ generated from precursor protein (APP) by sequential action β-secretase (BACE1) and γ-secretase. Although BACE1 distributed among various other tissues, its physiological substrates than APP have yet to be identified. ST6Gal I a sialyltransferase that produces sialylα2,6galactose residue, enzyme secreted out cell after proteolytic cleavage. We report here involved cleavage I,...
Abstract The β‐site amyloid precursor protein cleaving enzyme‐1 ( BACE 1), an essential protease for the generation of amyloid‐β (Aβ) peptide, is a major drug target Alzheimer's disease AD ). However, there concern that inhibiting 1 could also affect several physiological functions. Here, we show modified with bisecting N‐acetylglucosamine (Glc NA c), sugar modification highly expressed in brain, and demonstrate patients have higher levels Glc c on 1. Analysis knockout mice lacking...
Nucleotide sugars are important in determining cell surface glycoprotein glycosylation, which can modulate cellular properties such as growth and arrest. We have developed a conventional HPLC method for simultaneous determination of nucleotide sugars. A mixture (CMP-NeuAc, UDP-Gal, UDP-Glc, UDP-GalNAc, UDP-GlcNAc, GDP-Man, GDP-Fuc UDP-GlcUA) relevant nucleotides were perfectly separated an optimized ion-pair reversed-phase mode using Inertsil ODS-4 ODS-3 columns. The newly enabled us to...
Deposition of amyloid β (Aβ) in the brain is closely associated with Alzheimer disease (AD). Aβ generated from precursor protein (APP) by actions β- and γ-secretases. In addition to deposition parenchyma, cerebral vessel walls, termed angiopathy, observed more than 80% AD individuals. The mechanism for how accumulates blood vessels remains largely unknown. present study, we show that endothelial cells expressed APP770, a differently spliced APP mRNA isoform neuronal APP695, produced Aβ40...
Antiangiogenesis therapies are now part of the standard repertoire cancer therapies, but mechanisms for proliferation and survival endothelial cells not fully understood. Although covered with a glycocalyx, little is known about how glycosylation regulates functions. Here, we show that α2,6-sialic acid necessary cell-surface residency platelet cell adhesion molecule (PECAM), member immunoglobulin superfamily plays multiple roles in adhesion, mechanical stress sensing, antiapoptosis,...
Chronic obstructive pulmonary disease (COPD), manifested as emphysema and chronic airway obstruction, can be exacerbated by bacterial viral infections. Although the frequency of exacerbations increases progresses, mechanisms underlying this phenomenon are largely unknown, there is a need for simple in vivo exacerbation model. In study, we compared four groups mice treated with PBS alone, elastase LPS plus LPS. A single intratracheal administration to elastase-induced provoked infiltration...
β-Site amyloid precursor protein-cleaving enzyme-1 (BACE1) is a protease essential for amyloid-β (Aβ) production in Alzheimer's disease (AD). BACE1 protein known to be up-regulated by oxidative stress-inducing stimuli but the mechanism this up-regulation still needs clarified. We have recently found that modified with bisecting N-acetylglucosamine (GlcNAc) N-acetylglucosaminyltransferase-III (GnT-III, encoded Mgat3 gene) and GnT-III deficiency reduces Aβ-plaque formation brain accelerating...
BACE1 is a membrane-bound aspartic protease that cleaves the amyloid precursor protein (APP) at β-secretase site, critical step in Alzheimer disease pathogenesis. We previously found also cleaved sialyltransferase, ST6Gal I. By overexpression COS cells, secretion of I markedly increased, and amino terminus secreted started Glu41. Here we report BACE1-Fc chimera A-ST6Gal fusion protein, or I-derived peptide, between Leu37 Gln38, suggesting an initial cleavage product by was three acids longer...
β-Site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a membrane-bound aspartic protease that cleaves protein to produce neurotoxic peptide, Aβ, and implicated in triggering the pathogenesis of Alzheimer disease. We previously reported BACE1 cleaved rat β-galactoside α2,6-sialyltransferase (ST6Gal I) was overexpressed COS cells NH2 terminus ST6Gal I secreted from (E41 form) Glu41. Here we report gene knock-out mice have one third as much plasma control mice, indicating major which...
Abstract The proinflammatory cytokine interleukin (IL)‐1β is up‐regulated in microglial cells surrounding amyloid plaques, leading to the hypothesis that IL‐1β a risk factor for Alzheimer’s disease. However, we unexpectedly found significantly enhanced α‐cleavage, indicated by increases sAPPα and C83, but reduced β‐cleavage, decreases sAPPβ Aβ40/42, human neuroblastoma SK‐N‐SH cells. did not alter mRNA levels of BACE1, ADAM‐9, ADAM‐10, TACE threefold. proform mature form protein were also...
In demyelinating diseases such as multiple sclerosis, a critical problem is failure of remyelination, which important for protecting axons against degeneration and restoring conduction deficits. However, the underlying mechanism demyelination/remyelination remains unclear. <i>N</i>-acetylglucosaminyltransferase-IX (GnT-IX; also known GnT-Vb) brain-specific glycosyltransferase that catalyzes branched formation <i>O</i>-mannosyl glycan structures. <i>O</i>-Mannosylation α-dystroglycan its...
We previously demonstrated that a deficiency in core fucosylation caused by the genetic disruption of α1,6-fucosyltransferase (Fut8) leads to lethal abnormalities and development emphysematous lesions lung attenuation TGF-β1 receptor signaling. Herein, we investigated physiological relevance pathogenesis emphysema using viable heterozygous knock-out mice (Fut8(+/-)) were exposed cigarette smoke (CS). The Fut8(+/-) exhibited marked decrease FUT8 activity, matrix metalloproteinase (MMP)-9...
Abstract A series of N -glycans, each sequentially trimmed from biantennary sialoglycans, were homo- or heterogeneously clustered efficiently on fluorescent albumin using a method that combined strain-promoted alkyne-azide cyclization and 6π-azaelectrocyclization. Noninvasive in vivo kinetics dissection analysis revealed, for the first time, glycan-dependent shift urinary to gall bladder excretion mediated by sequential trimming non-reducing end sialic acids. -glycoalbumins further,...
Abstract Alzheimer's disease (AD) is characterized by amyloid‐β peptide (Aβ) deposition in the brain. Aβ produced sequential cleavage of amyloid precursor protein (APP) β‐secretase (BACE1: β‐site APP‐cleaving enzyme 1) and γ‐secretase. Previously, we demonstrated that BACE1 also cleaves β‐galactoside α2,6‐sialyltransferase (ST6Gal‐I) down‐regulates its transferase activity. Here, report overexpression ST6Gal‐I Neuro2a cells enhanced α2,6‐sialylation endogenous APP increased extracellular...
Most Alzheimer disease (AD) patients show deposition of amyloid β (Aβ) peptide in blood vessels as well the brain parenchyma. We previously found that vascular endothelial cells express precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since soluble cleavage product, sAPP, is considered to be possible marker for AD diagnosis, sAPP has been widely measured mixture these variants. hypothesized measurement APP770 product separately APP695 would enable...
Glycans play key roles in a variety of protein functions under normal and pathological conditions, but several glycosyltransferase-deficient mice exhibit no or only mild phenotypes due to redundancy compensation glycan functions. However, we have limited understanding the underlying mechanism for these observations. Our previous studies indicated that 70% Fut8-deficient (Fut8−/−) lack core fucose structure die within 3 days after birth, remainder survive up weeks although they show growth...
Expression of glycosyltransferase genes is essential for glycosylation. However, the detailed mechanisms how gene expression regulated in a specific tissue or during disease progression are poorly understood. In particular, epigenetic studies limited, although mechanisms, such as histone and DNA modifications, central to establish tissue-specific expression. We previously found that activation brain-specific N-acetylglucosaminyltransferase-IX (GnT-IX, also designated GnT-Vb), but mechanism...
Core fucosylation, a posttranslational modification of N-glycans, modifies several growth factor receptors and impacts on their ligand binding affinity. Core-fucose-deficient mice generated by ablating the α1,6 fucosyltransferase enzyme, Fut8, exhibit severe pulmonary emphysema, partly due to impaired macrophage function, similar aged Toll-like receptor 4 (Tlr4)-deficient mice. We therefore suspect that lack core fucose affects TLR4-dependent signaling pathway. Indeed, upon...