A5065826771- Endoplasmic Reticulum Stress and Disease
- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Cardiac electrophysiology and arrhythmias
- Amyotrophic Lateral Sclerosis Research
- Lung Cancer Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Atrial Fibrillation Management and Outcomes
- Acute Lymphoblastic Leukemia research
- Cholinesterase and Neurodegenerative Diseases
- Monoclonal and Polyclonal Antibodies Research
- Radiomics and Machine Learning in Medical Imaging
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Chronic Myeloid Leukemia Treatments
- Advanced X-ray and CT Imaging
- Pancreatic function and diabetes
- Hereditary Neurological Disorders
- Adenosine and Purinergic Signaling
- Neurogenetic and Muscular Disorders Research
- Venous Thromboembolism Diagnosis and Management
- Cardiac Arrhythmias and Treatments
- Calcium signaling and nucleotide metabolism
- Bacterial Infections and Vaccines
Niigata University Medical and Dental Hospital
2017-2024
Niigata University
2020-2024
Iwate Prefectural Central Hospital
2011-2024
Tokyo Metropolitan Institute of Medical Science
2023
Eisai (United States)
2021-2023
Keio University Hospital
2009-2023
Tokyo Medical and Dental University
2023
Nagoya University
2019-2022
Washington University in St. Louis
2016-2020
Stem Cell Institute
2019
Alzheimer's disease (AD) is the most common form of age-related dementia, characterized by progressive memory loss and cognitive disturbance. Mutations presenilin 1 (PS1) 2 (PS2) are causative factors for autosomal-dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC) technology can be used to model human disorders provide novel opportunities study cellular mechanisms establish therapeutic strategies against various diseases, including neurodegenerative diseases. Here...
Abstract Background Parkinson’s disease (PD) is a neurodegenerative characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form PD, PARK2, caused mutations parkin gene. -knockout mouse models show some abnormalities, but they do not fully recapitulate pathophysiology human PARK2. Results Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. iPSC-derived showed increased oxidative stress and enhanced activity...
The expansion of the GGGGCC hexanucleotide repeat in non-coding region Chromosome 9 open-reading frame 72 (C9orf72) gene is most common genetic cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This alteration leads to accumulation five types poly-dipeptides translated from repeat. Among these, poly-proline-arginine (poly-PR) poly-glycine-arginine (poly-GR) peptides are known be neurotoxic. However, mechanisms neurotoxicity associated with these not clear. A...
Neonatal diabetes is frequently part of a complex syndrome with extrapancreatic features: 18 genes causing syndromic neonatal have been identified to date. There are still patients who novel genetic syndromes. We performed exome sequencing in patient and his unrelated, unaffected parents identify the etiology characterized by diabetes, sensorineural deafness, congenital cataracts. Further testing was 311 diagnosed before 1 year age whom all known causes had excluded. 5 patients, including...
Induced pluripotent stem cell (iPSC) technology can be used to model human disorders, create cell-based models of diseases, including neurodegenerative and in establishing therapeutic strategies. To detect subtle cellular abnormalities associated with common late-onset disease iPSCs, valid control iPSCs derived from healthy donors free serious diseases are necessary. Here, we report the generation fibroblasts obtained immediately postmortem centenarian (106- 109-years-old) who were extremely...
Mutations in RNA-binding proteins, including fused sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43, encoded by TARDBP), are associated with sporadic familial amyotrophic lateral sclerosis. A major question is whether neuronal loss caused toxic gain-of-function cytoplasmic aggregates or of nuclear function. We generated a transgenic mouse overexpressing exogenous FUS without localization signal (ΔNLS-FUS), which developed progressive spastic motor deficits the cortex. The ΔNLS-FUS was...
Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) an ER-localized protein whose expression secretion induced by ER a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due lack knowledge receptor. Here we show that Neuroplastin (NPTN) such receptor for MANF. Biochemical analysis shows physiological...
A mutation in the ubiquilin 2 gene (UBQLN2) was recently identified as a cause of X-linked amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD) and major component inclusion bodies commonly found with wide variety ALS. ALS-linked mutations UBQLN2 are clustered unique proline-X-X repeat region, reportedly leading to impairment ubiquitin proteasome system. However, molecular properties mutant remain unclear. To gain insight into pathogenesis UBQLN2-linked ALS/FTD, we examined...
Abstract Cell-penetrating peptides (CPPs) including arginine-rich are attracting a lot of attention due to their potential as novel intracellular drug delivery tool without substantial toxicity. On the other hand, disease-associated CPPs, such poly-PR and poly-GR translated from C9orf72 gene, also efficiently enter neuronal cells then kill them. Although both non-harmful CPPs harmful poly-PR/GR penetrate plasma membrane using same arginine residues, little is known about factors which...
ABSTRACT Ligand-induced activation of epidermal growth factor receptor (EGFR) initiates trafficking events that re-localize the from cell surface to intracellular endocytic compartments. EGFR-containing endosomes are transported lysosomes for degradation by dynein–dynactin motor protein complex. However, this cargo-dependent endosomal mechanism remains largely uncharacterized. Here, we show GTP-bound Rab7 is phosphorylated on S72 leucine-rich repeat kinase 1 (LRRK1) at membrane. This...
Action potentials (APs) of the epicardial border zone (EBZ) cells from day 5 infarcted heart continue to be altered by 14 postocclusion, namely, they shortened. However, 2 mo, EBZ APs appear "normal," yet conduction wave fronts remains abnormal. We hypothesize that changes in transmembrane are due a change distribution ion channels either density or function. Thus we focused on Ca2+ and K+ currents isolated 14-day (IZ14d) 2-mo (IZ2m) compared them with those occurring same hearts but remote...
Heterozygosity for mutations (N88S and P90L) in the N-glycosylation site of seipin/BSCL2 is associated with autosomal dominant motor neuron diseases, spastic paraplegia 17 distal hereditary neuropathy type V, referred to as 'seipinopathies'.Previous vitro studies have shown that seipinopathy-linked result accumulation unfolded proteins endoplasmic reticulum (ER), leading protein response cell death, suggesting seipinopathies closely ER stress.To further understand molecular pathogenesis...
To determine the added value of combining intratumoral and peritumoral CT radiomics for prediction epidermal growth factor receptor (EGFR) gene mutations in primary lung cancer (PLC).This study included 478 patients with PLC (348 adenocarcinomas 130 other histological types) who underwent surgical resection EGFR testing. Two radiologists performed segmentation tumors regions using precontrast high-resolution images, 398 radiomic features (212 intra- 186 features) were extracted. The region...
Arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), translated from the hexanucleotide expansion in amyotrophic lateral sclerosis (ALS)-causative C9ORF72 gene, contribute significantly to pathogenesis of ALS. Although both R-DPRs share many similarities, there are critical differences their subcellular localization, phase separation, toxicity mechanisms. We analyzed protein-protein interactions, separation R-DPR variants found that sufficient segregation arginine charges...
Abstract Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations both endoplasmic reticulum (ER) and cytosolic free calcium levels known play a role cytokine-mediated death, there currently no treatments targeting cellular homeostasis combat Here we show that modulation can mitigate cytokine- ER stress-mediated death. The modulating compounds, dantrolene sitagliptin, prevent cytokine stress-induced...
Quantitative 3D Shape Analysis of CT Images Thymoma: A Comparison With Histological TypesMotohiko Yamazaki1, Kanako Oyanagi1, Hajime Umezu2, Takuya Yagi1, Hiroyuki Ishikawa1, Norihiko Yoshimura1 and Hidefumi Aoyama1Audio Available | Share
Objective: To determine whether INa and ICaL are altered in function/density right atrial (RA) cells from dogs with chronic fibrillation (cAF dogs, episodes lasting at least 6 days) the changes that occur differ those nonsustained or brief of (nAF dogs). Methods: Using whole cell voltage clamp, sodium calcium current density function were determined disaggregated RA nAF, cAF control atria (Con). Ca2+ currents studied either Ba2+ as charge carrier, well EGTA BAPTA internal solution chelator....