A5047653745- Cerebrovascular and genetic disorders
- Neurological Disease Mechanisms and Treatments
- S100 Proteins and Annexins
- RNA regulation and disease
- Neurological diseases and metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Moyamoya disease diagnosis and treatment
- Cerebrovascular and Carotid Artery Diseases
- Neurological Disorders and Treatments
- Alzheimer's disease research and treatments
- Connective Tissue Growth Factor Research
- Cell Adhesion Molecules Research
- Intracerebral and Subarachnoid Hemorrhage Research
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Neurological Complications and Syndromes
- RNA modifications and cancer
- RNA Research and Splicing
- Prion Diseases and Protein Misfolding
- Protease and Inhibitor Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Parkinson's Disease Mechanisms and Treatments
- Barrier Structure and Function Studies
- Drilling and Well Engineering
- Amyloidosis: Diagnosis, Treatment, Outcomes
Niigata University
2013-2023
Niigata City General Hospital
2020-2022
Niigata Prefectural Shibata Hospital
2021-2022
Tohoku University
2020
Mirai Hospital
2019
Juntendo University Shizuoka Hospital
2018
Kyushu University
2018
Kitano Hospital
2018
Komatsu (Japan)
2018
National Institute of Mental Health and Neurosciences
2017
The genetic cause of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which is characterized by ischemic, nonhypertensive, small-vessel disease associated alopecia spondylosis, unclear.In five families CARASIL, we carried out linkage analysis, fine mapping the region implicated in disease, sequence analysis a candidate gene. We also conducted functional wild-type mutant gene products measured signaling members transforming growth factor...
The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated.Clinical data from CSF1R mutation carriers who had seen at our institutions or reported elsewhere were collected analysed using a specific investigation sheet to standardize the data.In all, 122 cases 90 families mutations identified. mean age onset was 43 years (range 18-78 years), death 53...
<h3>Objective:</h3> To clarify the genetic, clinicopathologic, and neuroimaging characteristics of patients with hereditary diffuse leukoencephalopathy spheroids (HDLS) colony stimulating factor 1 receptor (<i>CSF-1R</i>) mutation. <h3>Methods:</h3> We performed molecular genetic analysis <i>CSF-1R</i> in HDLS. Detailed clinical findings were retrospectively investigated. Five examined neuropathologically. <h3>Results:</h3> found 6 different mutations 7 index from unrelated Japanese...
To elucidate the molecular mechanism of mutant HTRA1-dependent cerebral small vessel disease in heterozygous individuals.We recruited 113 unrelated index patients with clinically diagnosed disease. The coding sequences HTRA1 gene were analyzed. We evaluated protease activities using casein assays and oligomeric formation gel filtration chromatography.We found 4 missense mutations (p.G283E, p.P285L, p.R302Q, p.T319I) 6 from 2 siblings families p.R302Q. mean age at cognitive impairment onset...
<b>Background: </b> Spinocerebellar ataxia type 15 (SCA15) is a progressive neurodegenerative disorder characterized by pure cerebellar ataxia, very slow progression, and distinct atrophy. The locus for SCA15 was first mapped to 3p24.2-3pter in an Australian family. We have subsequently two Japanese families presenting with postural tremor of the head, arm, or trunk locus. Recently, partial deletions involving both 1 inositol 1,4,5-triphosphate receptor (<i>ITPR1</i>) sulfatase modifying...
Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis not well understood. We recently demonstrated that mutations the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause hereditary cerebral disease, autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). HTRA1 belongs to HTRA protein family, whose members have dual activities as chaperones proteases also repress transforming...
Background and purpose To establish validate diagnostic criteria for adult‐onset leukoencephalopathy with axonal spheroids pigmented glia ( ALSP ) due to colony‐stimulating factor 1 receptor CSF 1R mutation. Methods We developed based on a recent analysis of the clinical characteristics . These provide ‘probable’ ‘possible’ designations patients who do not have genetic diagnosis. verify its sensitivity specificity, we retrospectively applied our 83 cases had mutations (24 these were analyzed...
<h3>Objectives:</h3> The objective of this study was to clarify the characteristic brain MRI findings for genetically diagnosed CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). <h3>Methods:</h3> Seven patients carrying <i>HTRA1</i> mutations (representing 6 Japanese families) were included in study. Eighteen MRIs reviewed evaluated a new rating scale based on scoring abnormal hyperintense lesions atrophy. <h3>Results:</h3> At last...
<h3>SUMMARY:</h3> Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is a rare neurodegenerative disease resulting from mutations in the <i>colony stimulating factor 1 receptor</i> gene. Accurate diagnosis can be difficult because associated clinical MR imaging findings are nonspecific. We present 9 cases intracranial calcifications distributed 2 brain regions: frontal white matter adjacent to anterior horns of lateral ventricles parietal subcortical matter....
Frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are types of major TDP-43 (43-kDa TAR DNA-binding protein) proteinopathy. Cortical pathology has been analyzed in detail cases FTLD-TDP, but is still unclear ALS. We attempted to clarify the cortical subcortical Japanese sporadic ALS (n = 96) using an antibody specific phosphorylated (pTDP-43). The were divided into two groups: those without pTDP-43-positive neuronal cytoplasmic inclusions hippocampal dentate...
<i>Background:</i> Three major causative genes have been implicated as the cause of early-onset familial Alzheimer’s disease (AD): amyloid precursor protein gene <i>(APP)</i>, presenilin-1 <i>(PSEN1)</i> and <i>PSEN2</i>. Although rare, a tau-related dementia with mutations in microtubule-associated tau <i>(MAPT)</i> has identified patients showing clinical presentations similar to those AD. <i>Methods:</i> We performed...
Mutations in the PSEN1 gene encoding presenilin 1 (PS1) are linked to a vast majority of pedigrees with early-onset, autosomal dominant forms familial Alzheimer's disease (FAD). Lewy body (LB) pathology is frequently found brains FAD patients harboring mutations. We recently reported on novel PS1 mutation deletion threonine at codon 440 (ΔT440) case diagnosed as having neocortical type dementia LBs (DLB) and variant AD. In this report, we investigated possible involvement ΔT440 aberrant...
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is caused by mutations in CSF1R. Pathogenic exons 12-22 including coding sequence of the tyrosine kinase domain (TKD) CSF1R were previously identified. We aimed to identify patients who clinically suspected having ALSP determine pathogenicity novel variants.Sixty-one fulfilled diagnostic criteria included this study. Genetic analysis was performed for all exons. The haploinsufficiency examined frameshift RT-PCR....
Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal dominant neurodegenerative disorder caused by CAG repeat expansion. Previous studies demonstrated that the onset of DRPLA closely associated with length. However, natural history has not yet been evaluated. We here retrospectively investigated factors determine disease milestones and prognosis in 183 Japanese patients genetically diagnosed DRPLA. determined age at onset, which each subsequent clinical manifestations appeared,...
Background: Mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) cause cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Most carriers for HTRA1 mutations are asymptomatic, but more than 10 have been reported symptomatic carriers. The molecular differences between identified only CARASIL patients unclear. is a protease that forms homotrimers, each subunit activating adjacent via sensor domain of loop 3 (L3) activation...
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is a hereditary cerebral small vessel disease (CSVD) caused by homozygous or compound heterozygous mutations of the high temperature requirement A serine peptidase 1 gene ( HTRA1 ). Affected patients suffer from cognitive impairment, recurrent strokes, lumbago alopecia. Recently, clinical studies have indicated that some in may also CSVD. Here, we report histopathologic features an autopsied...
Objectives Clinical characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) include migraine, recurrent stroke, white matter lesions, vascular dementia. CADASIL is one the most common hereditary small vessel diseases. presentation varies a racial gap may exist between Asian Caucasian populations. This first nationwide epidemiological survey which aimed to elucidate clinical features in Japan. Moreover, registration database was...
Abstract Autosomal dominant spinocerebellar ataxias (AD‐SCAs) form a clinically and genetically heterogeneous group of neurodegenerative disorders. Recently, single nucleotide substitution in the 5′‐untranslated region puratrophin‐1 gene was found to be associated with one type AD‐SCA linked chromosome 16q (16q‐SCA). To obtain further insight into contribution C‐to‐T clinical genetic characteristics patients 16q‐SCA, we analyzed 686 families 719 individuals diagnosed progressive ataxia. We...
Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an autosomal-dominant disorder involving the cerebral, retinal, renal, and other systemic microvessels due to frameshift mutations in TREX1 gene. Under physiological conditions, protein localized cellular cytoplasm perinuclear area, but translocates into nucleus response oxidative DNA damage. It has been speculated that aberrant localization of may be associated microangiopathy patients RVCL. However, expression brain visceral...
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (MIM 600142) is linked to homozygous mutations in the high-temperature requirement A serine peptidase 1 gene ( HTRA1 ).1 The triad includes alopecia, spondylosis deformans, young-adult onset dementia following leukoaraiosis caused by cerebral small-vessel disease (CSVD).2 Although CARASIL originally was considered be a disorder monoethnic, restricted Japan, there are several reports of...