A5012313929- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Trace Elements in Health
- Multiple Sclerosis Research Studies
- Polyomavirus and related diseases
- Myasthenia Gravis and Thymoma
- Intracerebral and Subarachnoid Hemorrhage Research
- Peripheral Neuropathies and Disorders
- Dementia and Cognitive Impairment Research
- RNA regulation and disease
- Full-Duplex Wireless Communications
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Autoimmune Neurological Disorders and Treatments
- Parkinson's Disease and Spinal Disorders
- Balance, Gait, and Falls Prevention
- Cellular transport and secretion
- Plant Virus Research Studies
- Cerebral Palsy and Movement Disorders
- Neurosurgical Procedures and Complications
- Systemic Lupus Erythematosus Research
- Bacteriophages and microbial interactions
- Glioma Diagnosis and Treatment
- Cholinesterase and Neurodegenerative Diseases
Tokyo Medical and Dental University
2016-2025
Kudanzaka Hospital
2022-2025
Japan Pediatric Society
2024
San Francisco VA Medical Center
2024
University of California, San Francisco
2024
Tokyo Medical and Dental University Hospital
2023
Tohoku University
2020
Jichi Medical University
2020
Chiba East Hospital
2020
Tokushima University
2020
Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for therapeutic strategy disease.
Mutations in the PTEN-induced kinase 1 (PINK1) gene have recently been implicated autosomal recessive early onset Parkinson Disease (1, 2). To investigate role of PINK1 neurodegeneration, we designed human and murine neuronal cell lines expressing either wild-type or bearing a mutation associated with Disease. We show that under basal staurosporine-induced conditions, number terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells was lower SH-SY5Y than...
We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over past 10 years, since 1999. obtained information on 1685 Japanese suspected as having judged 1222 diseases, consisting definite (n = 180, 14.7%) probable 1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt–Jakob disease which also included possible cases 13, 1.1%). They were classified into 922...
Introduction The definitive diagnosis of genetic prion diseases (gPrD) requires pathological confirmation. To date, has relied upon the finding biomarkers 14-3-3 protein and total tau (t-tau) in cerebrospinal fluid (CSF), but many researchers have reported that these markers are not sufficiently elevated gPrD, especially Gerstmann-Sträussler-Scheinker syndrome (GSS). We recently developed a new vitro amplification technology, designated "real-time quaking-induced conversion (RT-QUIC)", to...
To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers onset of disease.We assembled age at or death data from 1,094 individuals with high penetrance mutations the protein gene (PRNP) order generate survival and hazard curves test for modifiers onset. We used formulae simulations estimate statistical power clinical trials.Genetic varies over several decades most common neither sex, parent's onset, nor PRNP codon 129...
Midkine (MK) is a new member of the heparin-binding neurotrophic factor family. MK plays important roles in development and carcinogenesis has several biological effects, including promotion neurite extension neuronal survival. However, mechanism by which exerts its actions on neurons not been elucidated to date. We have established an apoptosis induction system serum deprivation primary cultures isolated from mouse cerebral cortices. Neuronal induced was accompanied activation caspase-3....
APH-1 and PEN-2 genes modulate the function of nicastrin presenilins in <i>Caenorhabditis elegans</i>. Preliminary studies transfected mammalian cells overexpressing tagged proteins suggest that this genetic interaction is mediated by a direct physical interaction. Using protein encoded on human chromosome 1 (APH-1<sub>1</sub>L; also known as APH-1a) an archetype, we report here endogenous forms are predominantly expressed intracellular membrane compartments, including endoplasmic reticulum...
Background and Purpose— Cellular origin of apolipoprotein E (ApoE) in the human brain its roles physiological pathological conditions remain to be clarified. Methods— Immunolocalization ApoE was investigated a series autopsied brains with or without infarction. expression also estimated on immunoblot protein extracts from cultured neuroblastoma cell line (GOTO) subjected an oxidative stress induced by exposure hydrogen peroxide (0.2 mmol/L). Results— In addition astrocytes microglia, neurons...
Several lines of evidence have indicated that the presenilin proteins function within macromolecular complexes and are necessary for regulated intramembranous proteolysis certain type 1 transmembrane proteins, including amyloid precursor protein, Notch, p75. Data from multiple complementary experiments now suggest there may be several distinct complexes. We show here mutations detergents affect abundance componentry complexes, these structural effects correlate with their on γ-secretase...
Objectives Genetic Creutzfeldt-Jakob disease (CJD) due to V180I mutation in the prion protein gene ( PRNP ) is of great interest because differences from sporadic CJD and other genetic diseases terms clinical features, as well pathological biochemical findings. However, few systematic observations about features patients with this unique have been published. Therefore, goal study was relate forms a perspective. Design We analysed symptoms, genetics, biomarkers cerebrospinal fluid (CSF) MRI...
Abstract Background Although a large amount of evidence has revealed that amyloid β (Aβ), especially Aβ oligomers, protofibrils, and pyroglutamated Aβs, participate primarily in the pathophysiological processes Alzheimer’s disease, most clinical trials anti-Aβ antibody therapy have never acquired successful efficacy human trials, partly because peripheral administration medications was unable to deliver sufficient amounts molecules brain. Recently, we developed polymeric nanomicelles capable...
Presenilin 1 or presenilin 2, nicastrin, APH-1, and PEN-2 form high molecular weight complexes that play a pivotal role in the cleavage of various Type I transmembrane proteins, including beta-amyloid precursor protein. The specific function is unclear. To explore its intermolecular interactions, we conducted deletion mutagenesis studies on series conserved residues at C terminus PEN-2. These suggest that: 1) both presence amino acid sequence DYLSF domain (residues 90-94) critical for...
A national system for surveillance of prion diseases (PrDs) was established in Japan April 1999. Here, we analyzed the relationships among protein gene (PRNP) mutations and clinical features, cerebrospinal fluid (CSF) markers, pathological characteristics major genotypes genetic PrDs (gPrDs). We retrospectively age at onset disease duration; concentrations incidences 14-3-3 protein, tau abnormal (PrPSc) CSF 309 gPrD patients with P102L, P105L, E200K, V180I, or M232R mutations; brain...
Abstract Objective Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the impact of amyloid PET imaging is still under investigation. The aim this study was to evaluate diagnostic utility in patient management using 18 F-florbetapir patients with cognitive impairment suspected Alzheimer’s disease (AD). We also aimed determine cutoffs positivity quantitative measures by investigating agreement between...
Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML non-reportable few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) performed at National Institute of Infectious Diseases to support diagnosis. To clarify overall profile patient data provided time CSF-JCV over 10...
An early diagnosis is required for intervention in prion disease cases. To elucidate the specificity of electroencephalography discharges cases sporadic Creutzfeldt-Jakob disease, we analysed epileptiform through electroencephalography. Nine patients with methionine/methionine type 1/classic and 20 status epilepticus were included. Generalized periodic discharges, lateralized central sagittal evaluated. Central defined as nonrhythmic nonperiodic waveforms showing generalized spike-and-wave...
<h3>Objective</h3> More than 60% of patients worldwide with Creutzfeldt-Jakob disease (CJD) associated dura mater graft (dCJD) have been diagnosed in Japan. The remarkable frequency grafts Japan may possibly contribute to the elevated incidence dCJD, but reasons for disproportionate use this procedure remain unclear. We investigated differences between dCJD and those elsewhere help explain more frequent cadaveric high <h3>Methods</h3> obtained data on from Japanese national CJD surveillance...
The Brief International Cognitive Assessment for MS (BICAMS) is a practical battery measuring cognitive function in multiple sclerosis (MS).We aimed to validate Japanese version of the BICAMS patients with and healthy controls.The Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-Second Edition (CVLT2) Visuospatial Memory Revised (BVMTR) were administered 156 126 controls (HCs). was re-administered subset 27 30 HCs.The mean (±SD) raw scores HC groups as follows: SDMT: 47.9...
Accelerometry-based gait analysis is a promising approach in obtaining insightful information on the characteristics of patients with neurological disorders such as dementia and Parkinson's disease (PD). In order to improve its practical use outside laboratory or hospital, it required design new metrics capable quantifying ambulatory their extraction procedures from long-term acceleration data. This paper presents method developed for purpose. Our system based single trunk-mounted...
Objective To clinically diagnose MM2-cortical (MM2C) and MM2-thalamic (MM2T)-type sporadic Creutzfeldt-Jakob disease (sCJD) at early stage with high sensitivity specificity. Methods We reviewed the results of Surveillance Study in Japan between April 1999 September 2019, which included 254 patients pathologically confirmed prion diseases, including 9 MM2C-type sCJD (MM2C-sCJD) 10 MM2T-type (MM2T-sCJD), 607 non-prion diseases. Results According to conventional criteria sCJD, 4 MM2C- 7...
Presenilin-1 (PSEN1) is a primary component of the γ-secretase complex, and total levels its holoprotein endoproteolytic fragments are tightly regulated. We examined effects several types endoplasmic reticulum (ER) stress on quantita