A5081055613- Lysosomal Storage Disorders Research
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Genetics and Neurodevelopmental Disorders
- Trypanosoma species research and implications
- Cellular transport and secretion
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Autism Spectrum Disorder Research
- Genetic Neurodegenerative Diseases
- Tuberous Sclerosis Complex Research
- Mitochondrial Function and Pathology
- Polyomavirus and related diseases
- Glycogen Storage Diseases and Myoclonus
- Parkinson's Disease Mechanisms and Treatments
- Porphyrin Metabolism and Disorders
- Endoplasmic Reticulum Stress and Disease
- Folate and B Vitamins Research
- Biochemical and Molecular Research
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- Heme Oxygenase-1 and Carbon Monoxide
- Aortic Disease and Treatment Approaches
- Biomedical Research and Pathophysiology
- Connective tissue disorders research
Tottori University
2015-2024
Tottori University Hospital
2000-2022
Global Strategy Group
2019
National Institute of Technology, Yonago College
2014-2019
Genomics (United Kingdom)
2005-2016
Research Institute for Bioscience and Biotechnology
2014-2015
Faculty (United Kingdom)
2014
National Center of Neurology and Psychiatry
1987-2003
Seikagaku Corporation (Japan)
2003
National Institute of Infectious Diseases
2003
Abstract Objective Gaucher disease (GD) is a lysosomal storage characterized by deficiency of glucocerebrosidase. Although enzyme‐replacement and substrate‐reduction therapies are available, their efficacies in treating the neurological manifestations GD negligible. Pharmacological chaperone therapy hypothesized to offer new strategy for this disease. Specifically, ambroxol, commonly used expectorant, has been proposed as candidate pharmacological chaperone. The purpose study was evaluate...
The aim of the present study was to assess contribution polymorphisms in breast cancer resistance protein/ATP-binding cassette transporter G2 (<i>BCRP/ABCG2</i>) gene placental expression from a new perspective, allelic imbalance. Polymorphisms were screened by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis followed sequencing with DNA extracted 100 placentas. To examine whether <i>BCRP</i> correlate BCRP expression, we determined mRNA and protein levels...
We synthesized a galactose derivative, N- octyl-4-epi-β-valienamine (NOEV), for molecular therapy (chemical chaperone therapy) of human neurogenetic disease, β-galactosidosis (G M1 -gangliosidosis and Morquio B disease). It is potent inhibitor lysosomal β-galactosidase in vitro . Addition NOEV the culture medium restored mutant enzyme activity cultured or murine fibroblasts at low intracellular concentrations, resulting marked decrease substrate storage. Short-term oral administration to...
CGG repeat–derived RNA G-quadruplexes accelerate liquid-to-solid transition of FMRpolyG.
Mouse knockout models have clearly demonstrated the critical importance of IGF-I and IGF receptor type 1 (IGF-IR) for embryonic growth as well postnatal growth.We hypothesized that mutations IGF-IR gene might predispose to short stature in children born with intrauterine retardation (IUGR).Twenty-four unexplained IUGR (birth weight < -1.5 SD) (<-2.0 were screened abnormalities gene.Direct DNA sequencing was used identify mutations. Unprocessed proreceptor fibroblasts detected by immunoblot...
Autism is a severe neurodevelopmental disorder of early childhood. Genetic factors play an important role in the aetiology disorder. In this study, we considered NRCAM gene as candidate autism. This expressed central nervous system and located 7q region, susceptibility locus We conducted case-control study 18 single nucleotide polymorphisms (SNPs) within for possible association with autism 170 autistic patients 214 normal controls Japanese population. Seven SNPs were significantly...
The production of cells capable expressing gene(s) interest is important for a variety applications in biomedicine and biotechnology, including gene therapy animal transgenesis. ability to insert transgenes at precise location the genome, using site-specific recombinases such as Cre, FLP, ΦC31, has major benefits efficiency Recent work on integrases from R4, TP901-1 Bxb1 phages demonstrated that these catalyze recombination mammalian cells. In present study, we examined activities expression...
Approximately half of autism spectrum disorder (ASD) individual suffer from comorbid intellectual disabilities (ID). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and likely to play a modulatory role excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that the representative group Kanner type ASD subjects OXT could have beneficial effect social communication interaction. The aim this pilot study was investigate feasibility...
Lysosomal β-galactosidase (β-Gal) deficiency causes a group of disorders that include neuronopathic GM1 gangliosidosis and non-neuronopathic Morquio B disease. We have previously proposed the use small molecule ligands β-Gal as pharmacological chaperones (PCs) for treatment brain pathology. Although it is still under development, PC therapy has yielded promising preclinical results in several lysosomal diseases. In this study, we evaluated effect bicyclic 1-deoxygalactonojirimycin (DGJ)...
Abstract A general approach is reported for the design of small‐molecule competitive inhibitors lysosomal glycosidases programmed to 1) promote correct folding mutant enzymes at endoplasmic reticulum, 2) facilitate trafficking, and 3) undergo dissociation self‐inactivation lysosome. The strategy based on incorporation an orthoester segment into iminosugar conjugates switch nature aglycone moiety from hydrophobic hydrophilic in pH 7 5 window, which has a dramatic effect enzyme binding...
The identification of causative genetic variants for hereditary diseases has revolutionized clinical medicine and an extensive collaborative framework with international cooperation become a global trend to understand rare disorders. Initiative on Rare Undiagnosed Diseases (IRUD) was established in Japan provide accurate diagnosis, discover causes, ultimately cures undiagnosed diseases. fundamental IRUD system consists three pillars: diagnostic coordination, analysis centers (IRUD-ACs), data...
Imai, Jun; Ieiri, Ichiro; Mamiya, Kohsuke; Miyahara, Sayaka; Furuumi, Hiroyasu; Nanba, Eiji; Yamane, Masayuki; Fukumaki, Yasuyuki; Ninomiya, Hideaki; Tashiro, Nobutada; Otsubo, Kenji; Higuchi, Shun Author Information
Abstract Niemann–Pick type C disease is a neurovisceral storage disorder. Neurofibrillary tangles similar to those in Alzheimer's have been reported most juvenile/adult patients without amyloid β protein (Aβ) deposits. Recently, we found deposits of Aβ the form diffuse plaques three (31‐ and 32‐year‐old sisters 37‐year‐old man) nine patients, who presented with severe tauopathy numerous neurofibrillary tangles. were not detected any control brains younger than age 42 years. These deposit all...
Competitive inhibitors of either α-galactosidase (α-Gal) or β-galactosidase (β-Gal) with high affinity and selectivity have been accessed by exploiting aglycone interactions conformationally locked sp2-iminosugars. Selected compounds were profiled as potent pharmacological chaperones for mutant lysosomal α- β-Gal associated Fabry disease GM1 gangliosidosis.
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the GLA gene often leading to missense α-galactosidase A (α-Gal A) variants that undergo premature endoplasmic reticulum-associated degradation due folding defects. We have synthesized and characterized a new family of neutral amphiphilic pharmacological chaperones, namely 1-deoxygalactonojirimycin-arylthioureas (DGJ-ArTs), capable stabilizing α-Gal restoring trafficking. Binding enzyme reinforced strong...