A5039543515- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- Muscle Physiology and Disorders
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Hereditary Neurological Disorders
- Neurological disorders and treatments
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Peripheral Neuropathies and Disorders
- Nerve injury and regeneration
- Botulinum Toxin and Related Neurological Disorders
- Neurological diseases and metabolism
- Inflammatory Myopathies and Dermatomyositis
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Acute Ischemic Stroke Management
- Heat shock proteins research
- Neurological and metabolic disorders
- 3D Printing in Biomedical Research
- Axon Guidance and Neuronal Signaling
Aichi Medical University
2016-2025
Japan Pediatric Society
2024
Nagoya University
2000-2020
Niigata University
2001-2020
Keio University
2020
Tokyo Medical and Dental University
2020
University School
2020
Aichi Medical University Hospital
2014-2019
Institut Européen de Chimie et Biologie
2001
École Polytechnique
2001
Through functional expression screening, we identified a gene, designated Humanin (HN) cDNA, which encodes short polypeptide and abolishes death of neuronal cells caused by multiple different types familial Alzheimer's disease genes Aβ amyloid, without effect on Q79 or superoxide dismutase-1 mutants. Transfected HN cDNA was transcribed to the corresponding then secreted into cultured medium. The rescue action clearly depended primary structure HN. This would serve as molecular clue for...
Our objective was to confirm the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients. We conducted a 36-week confirmatory study, consisting 12-week pre-observation period followed by 24-week treatment period. Patients received placebo or i.v. infusion over 60 min for first 14 days cycle 1, 10 during cycles 2 6. The primary endpoint changed revised ALS functional rating scale (ALSFRS-R) scores treatment. were treated with (n = 104) 102). Changes ALSFRS-R −6.35 ±...
Abstract Spinal and bulbar muscular atrophy (SBMA) is an X‐linked motor neuronopathy caused by the expansion of unstable CAG repeat in coding region androgen receptor (AR) gene. To study AR protein expression normal SBMA individuals, we used several antibodies that recognize protein, analyzed neural nonneural tissues immunohistochemistry western blotting. Both mutant proteins were widely distributed, predominantly, but not exclusively, cytoplasm neurons regardless pathological involvement,...
Spinal and bulbar muscular atrophy (SBMA) is one of a group human inherited neurodegenerative diseases caused by polyglutamine expansion. We have previously demonstrated that the SBMA gene product, androgen receptor protein, toxic aggregates when truncated. Heat shock proteins function as molecular chaperones, which recognize renaturate misfolded protein (aggregate). thus assessed effect variety chaperones in cultured neuronal cell model SBMA. Overexpression reduces aggregate formation...
Familial amyotrophic lateral sclerosis (FALS)-linked mutations in copper-zinc superoxide dismutase (SOD1) cause motor neuron death through one or more acquired toxic properties. We analyzed the molecular mechanism underlying degeneration transgenic mouse model expressing SOD1 gene with G93A mutation. Using cDNA microarray, differentially expressed genes were identified spinal cords of mice, 30 being elevated and seven decreased. microarray analysis to monitor expression during...
Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of polyglutamine (polyQ) tract within androgen receptor (AR). The nuclear inclusions consisting mutant AR protein are characteristic combine with many components ubiquitin–proteasome molecular chaperone pathways, raising possibility that misfolding altered degradation may be involved in pathogenesis. We have reported overexpression heat shock (HSP) chaperones reduces aggregation cell death...
Abstract The causative pathomechanism of sporadic amyotrophic lateral sclerosis (ALS) is not clearly understood. Using microarray technology combined with laser‐captured microdissection, gene expression profiles degenerating spinal motor neurons isolated from autopsied patients ALS were examined. Gene was quantitatively assessed by real‐time reverse transcription polymerase chain reaction and in situ hybridization. Spinal showed a distinct profile the whole ventral horn. Three percent genes...
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by the expansion of a trinucleotide CAG repeat encoding polyglutamine tract in first exon androgen receptor gene ( AR ). The pathogenic, polyglutamine-expanded protein accumulates cell nucleus ligand-dependent manner inhibits transcription interfering with transcriptional factors coactivators. Heat-shock proteins (HSPs) are stress-induced chaperones that facilitate refolding and, thus, degradation...
Machado--Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration mapped to chromosome 14q32.1. The CAG expansions of the MJD1 gene was identified as cause disease. We have analyzed 90 MJD individuals from 62 independent families and found that repeat length inversely correlated with age onset (r = -0.87). chromosomes contained 61-84 units, whereas normal displayed 14-34 repeats. In chromosomes, 14 units were most common shortest. association clinical anticipation disease,...
Abstract The genetic mutation of X‐linked recessive bulbospinal neuronopathy is amplification a polymorphic tandem CAG repeat in the androgen receptor gene. We studied this 26 Japanese patients from 21 families with neuronopathy. number repeats was significantly correlated age at onset limb muscular weakness ( r = −0.596, p < 0.001) and age‐adjusted scored disability 0.446, 0.03). length therefore seems to be determinant factor clinical severity.
Amyotrophic lateral sclerosis (ALS) is a progressive paralytic disorder resulting from the degeneration of motor neurons in cerebral cortex, brainstem, and spinal cord. The cytopathological hallmark remaining ALS presence ubiquitylated inclusions consisting insoluble protein aggregates. In this paper we report that Dorfin, RING finger-type E3 ubiquitin ligase, predominantly localized inclusion bodies familial with copper/zinc superoxide dismutase (SOD1) mutation as well sporadic ALS. Dorfin...
Mutations in the Cu/Zn-superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS) through gain of a toxic function; however, nature this function remains largely unknown. Ubiquitylated aggregates mutant SOD1 proteins affected brain lesions are pathological hallmarks disease and suggested to be involved several proposed mechanisms motor neuron death. Recent studies suggest that readily forms an incorrect disulfide bond upon mild oxidative stress vitro, insoluble...
Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of polyglutamine tract in androgen receptor (AR). Animal studies have shown that pathogenesis SBMA dependent on serum testosterone level. This study aimed at evaluating efficacy safety deprivation leuprorelin acetate patients with SBMA.Fifty underwent subcutaneous injections or placebo randomized, placebo-controlled trial for 48 weeks, followed an open-label additional 96 which 19 group 15...
Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine tract within androgen receptor (AR). The pathologic features SBMA are loss in spinal cord brainstem diffuse nuclear accumulation inclusions mutant AR residual neurons certain visceral organs. Many components ubiquitin-proteasome molecular chaperones also sequestered inclusions, suggesting that they may be actively engaged attempt to degrade or refold AR. C terminus Hsc70...
The mutations in superoxide dismutase 1 (SOD1) cause ∼20% of familial amyotrophic lateral sclerosis cases. A toxic gain function has been considered to be the disease, but its molecular mechanism remains uncertain. To determine whether subcellular localization mutant SOD1 is crucial SOD1-mediated cell death, we produced neuronal models with accumulation each fraction/organelle, such as cytosol, nucleus, endoplasmic reticulum, and mitochondria. We showed that mitochondria triggered release...
Spinal and bulbar muscular atrophy is an X-linked motor neuronopathy caused by the expansion of unstable CAG repeat in coding region androgen receptor (AR) gene. Nuclear inclusions mutant AR protein have been shown to occur spinal neurons (Li M, Kobayashi Y, Merry D, Tanaka F, Doyu Hashizume Fischbeck KH, Sobue G: atrophy. Ann Neurol 1998 (in press)). In this study, we demonstrate tissue-specific distribution, immunochemical features, fine structure nuclear were observed affected brainstem...
Spinal and bulbar muscular atrophy (SBMA) is a hereditary neurodegenerative disease caused by an expansion of trinucleotide CAG repeat encoding the polyglutamine tract in androgen receptor ( AR ) gene. To elucidate pathogenesis polyglutamine-mediated motor neuron dysfunction, we investigated histopathological biological alterations transgenic mouse model SBMA carrying human pathogenic AR. In affected mice, neurofilaments synaptophysin accumulated at distal axon. A similar intramuscular...
Human pluripotent stem cells (hPSCs) are being applied in regenerative medicine and for the vitro modeling of human intractable disorders. In particular, neural derived from disease-specific induced (hiPSCs) established patients with neurological disorders have been used as disease models to recapitulate vivo pathogenesis because cannot be usually obtained themselves. this study, we a rapid, efficient, simple method efficiently deriving motor neurons hPSCs that is useful pathophysiological...
<h3>Objective:</h3> To reveal characteristic clinicopathological correlates of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome. <h3>Methods:</h3> The clinical features 22 patients with POEMS syndrome were investigated correlated the histopathological sural nerves serum cytokine profiles. <h3>Results:</h3> More than half complained pain in lower extremities, which is closely related to hyperalgesia. Assessment total nerve fibre population...