研究者詳細 - 小野寺　理

Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein 査読

Y Sano, H Date, S Igarashi, O Onodera, M Oyake, T Takahashi, S Hayashi, M Morimatsu, H Takahashi, T Makifuchi, N Fukuhara, S Tsuji

ANNALS OF NEUROLOGY 55 ( 2 ) 241 - 249 2004年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is an autosomal recessive neurodegenerative disorder characterized by early-onset ataxia, ocular motor apraxia, and hypoalbuminemia. Recently, the causative gene for EAOH, APTX, has been identified. Of the two splicing variants of APTX mRNA, the short and the long forms, long-form APTX mRNA was found to be the major isoform. Aprataxin is mainly located in the nucleus, and, furthermore, the first nuclear localization signal located near the amino terminus of the long-form aprataxin is essential for its nuclear localization. We found, based on the yeast two-hybrid and coimmunoprecipitation experiments, that the long-form but not the short-form aprataxin interacts with XRCC1 (x-ray repair cross-complementing group 1). Interestingly the amino terminus of the long-form aprataxin is homologous with polynucleotidekinase-3'-phosphatase, which has been demonstrated to be involved in base excision repair, a subtype of single-strand DNA break repair, through interaction with XRCC1, DNA polymerase beta, and DNA ligase III. These results strongly support the possibility that aprataxin and XRCC1 constitute a multiprotein complex and are involved in single-strand DNA break repair, and furthermore, that accumulation of unrepaired damaged DNA underlies the pathophysiological mechanisms of EAOH.

DOI： 10.1002/ana.10808

SCA17 homozygote showing Huntington's disease-like phenotype 査読

Y Toyoshima, M Yamada, O Onodera, M Shimohata, C Inenaga, N Fujita, M Morita, S Tsuji, H Takahashi

ANNALS OF NEUROLOGY 55 ( 2 ) 281 - 286 2004年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

We report a homozygous case of spinocerebellar ataxia type 17 with 48 glutamines. The age of the patient at disease onset was not lower than those of heterozygotes with the same CAG-repeat sizes, but the clinical manifestations were rapidly progressive dementia and chorea. Neuronal loss was relatively restricted and most prominent in the Purkinje cell layer and striatum; however, intranuclear neuronal polyglutamine accumulation was widespread, with a high frequency in the cerebral cortex and striatum.

DOI： 10.1002/ana.10824

Spinocerebellar ataxia type 17 repeat in patients with huntington's disease-like and ataxia [1] (multiple letters)

Cellini, E., Forleo, P., Nacmias, B., Tedde, A., Bagnoli, S., Piacentini, S., Sorbi, S., Toyoshima, Y., Yamada, M., Onodera, O., Shimohata, M., Inenaga, C., Fujita, N., Morita, M., Tsuji, S., Takahashi, H.

Annals of Neurology 56 ( 1 ) 2004年

Two Cases of Generalized Tetanus Presenting with Dysphagia as an Initial Symptom 査読

Masato Kanazawa, Hideaki Ishiguro, Osamu Onodera, Kenjiro Yoshikawa, Takashi Koide, Aki Arai, Arika Hasegawa, Ryouichi Nakano, Keiko Tanaka, Masatoyo Nishizawa

Brain and Nerve 55 ( 11 ) 973 - 976 2003年11月

記述言語：日本語掲載種別：研究論文（学術雑誌）

We describe two patients with generalized tetanus, a 60-year-old man and a 76-year-old woman, presenting with dysphagia as an initial symptom of the disease. Eighty percent of patients with generalized tetanus manifest dysphagia on admission to a hospital. However, dysphagia is rare as an initial symptom. Both our patients had dysphagia as their initial symptom, followed by neck stiffness and trismus. We made a diagnosis of generalized tetanus based on these neurological findings in the absence of an apparent episode of trauma. After the administration of tetanus immunoglobulin on admission, they recovered without exhibiting generalized convulsion, autonomic storm, or any other serious complications. The vaccination of tetanus toxoid cannot maintain sufficient antibody titers more than ten years. Therefore, elderly people are considered susceptible to tetanus. We suggest that tetanus should be considered in the differential diagnosis of dysphagia particularly in elderly patients. We also suggest that treatment of tetanus should be initiated immediately, because tetanus still has a high mortality rate at present.

Scopus

Severe generalized dystonia as a presentation of a patient with aprataxin gene mutation 査読

Y Sekijima, T Hashimoto, O Onodera, H Date, T Okano, K Naito, S Tsuji, S Ikeda

MOVEMENT DISORDERS 18 ( 10 ) 1198 - 1200 2003年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

A 14-year-old girl, homozygous for an insertion mutation of aprataxin (APTX), 689 ins T, is described. She presented with severe generalized dystonia, ataxia, ocular motor apraxia, and areflexia. The dystonia of this patient suggests involvement of the basal ganglia or thalamus, along with clinical diversity in this disorder. 0 2003 Movement Disorder Society.

DOI： 10.1002/mds.10526

[Steroid-pulse therapy in Guillain-Barré syndrome associated with cytomegalovirus infection: a case report]. 査読

Tada M, Onodera O, Kawachi I, Hara K, Sato M, Yoshino H, Asano A, Soma Y, Tsuji S

No to shinkei = Brain and nerve 55 ( 7 ) 615 - 621 2003年7月

Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients 査読

N Hattori, M Yamamoto, T Yoshihara, H Koike, M Nakagawa, H Yoshikawa, A Ohnishi, K Hayasaka, O Onodera, M Baba, H Yasuda, T Saito, K Nakashima, J Kira, R Kaji, N Oka, G Sobue

BRAIN 126 ( Pt 1 ) 134 - 151 2003年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：OXFORD UNIV PRESS

Three genes commonly causing Charcot-Marie-Tooth disease (CMT) encode myelin-related proteins: peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ) and connexin 32 (Cx32). Demyelinating versus axonal phenotypes are major issues in CMT associated with mutations of these genes. We electrophysiologically, pathologically and genetically evaluated demyelinating and axonal features of 205 Japanese patients with PMP22 duplication, MPZ mutations or Cx32 mutations. PMP22 duplication caused mainly demyelinating phenotypes with slowed motor nerve conduction velocity (MCV) and demyelinating histopathology, while axonal features were variably present. Two distinctive phenotypic subgroups were present in patients with MPZ mutations: one showed preserved MCV and exclusively axonal pathological features, while the other was exclusively demyelinating. These axonal and demyelinating phenotypes were well concordant among siblings in individual families, and MPZ mutations did not overlap among these two subgroups, suggesting that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. Patients with Cx32 mutations showed intermediate slowing of MCV, predominantly axonal features and relatively mild demyelinating pathology. These axonal and demyelinating features were present concomitantly in individual patients to a variable extent. The relative severity of axonal and demyelinating features was not associated with particular Cx32 mutations. Median nerve MCV and overall histopathological phenotype changed little with disease advancement. Axonal features of diminished amplitudes of compound muscle action potentials (CMAPs), axonal loss, axonal sprouting and neuropathic muscle wasting all changed as disease advanced, especially in PMP22 duplication and Cx32 mutations. Median nerve MCVs were well maintained independently of age, disease duration and the severity of clinical and pathological abnormalities, confirming that median nerve MCV is an excellent marker for the genetically determined neuropathic phenotypes. Amplitude of CMAPs was correlated significantly with distal muscle strength in PMP22 duplication, MPZ mutations and Cx32 mutations, while MCV slowing was not, indicating that clinical weakness results from reduced numbers of functional large axons, not from demyelination. Thus, the three major myelin-related protein mutations induced varied degrees of axonal and demyelinating phenotypic features according to the specific gene mutation as well as the stage of disease advancement, while clinically evident muscle wasting was attributable to loss of functioning large axons.

DOI： 10.1093/brain/awg012

Current states of molecular diagnosis of neurodegenerative disorders

Onodera, O.

Japanese Journal of Clinical Radiology 48 ( 4 ) 2003年

A study of shock wave interaction with a rotating cylinder

Sun, M., Yada, K., Jagadeesh, G., Onodera, O., Ogawa, T., Takayama, K.

Shock Waves 12 ( 6 ) 2003年

皮質基底核変性症(CBD)と進行性核上性麻痺(PSP)の病理診断基準

若林孝一, 高橋均, 高橋均, 小野寺理, 西澤正豊

臨床神経学 42 ( 11 ) 1155 - 1157 2002年11月

記述言語：日本語出版者・発行元：Societas Neurologica Japonica

TDP-43はRNA代謝に関連する核内蛋白である．その機能低下によるRNA代謝異常が，代表的な成人運動ニューロン疾患である筋萎縮性側索硬化症（Amyotrophic lateral sclerosis; ALS）病態機序の一つとして提唱されている．われわれはALS罹患神経組織において，TDP-43機能低下に由来した，核内小体の一種GEM小体数および機能性RNA蛋白複合体minor spliceosomesの発現低下がみられる事を報告した．同様の現象は小児運動ニューロン疾患である脊髄性筋無力症（spinal muscular atrophy）でもみとめられることから，運動ニューロン疾患における選択的神経変性において重要な役割をはたしている可能性がある．

DOI： 10.5692/clinicalneurol.54.1155

CiNii Article

CiNii Books

その他リンク： https://jlc.jst.go.jp/DN/JLC/20005129827?from=CiNii

Japanese cases of familial hemiplegic migraine with cerebellar ataxia carrying a T666M mutation in the CACNA1A gene 査読

T Takahashi, S Igarashi, T Kimura, Hozumi, I, Kawachi, I, O Onodera, H Takano, M Saito, S Tsuji

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY 72 ( 5 ) 676 - 677 2002年5月

Expanded polyglutamine stretches form an 'aggresome' 査読

T Shimohata, A Sato, Burke, JR, WJ Strittmatter, S Tsuji, O Onodera

NEUROSCIENCE LETTERS 323 ( 3 ) 215 - 218 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI IRELAND LTD

To understand the pathogenetic mechanisms underlying polyglutamine (polyQ) diseases, we investigated the mechanisms of the formation of aggregate bodies containing expanded polyQ stretches, focusing on dentatorubral-pallidoluysian atrophy (DRPLA). We demonstrated that the expression of a truncated DRPLA protein containing expanded polyQ stretches in COS-7 cells resulted in the formation of perinuclear aggregate bodies that are co-localized with gamma-tubulin, a protein marker for the microtubules-organizing center (MTOC). A collapsed vimentin network surrounded these aggregate bodies. Furthermore, disruption of the microtubules (MTs) with nocodazole resulted in the formation of small aggregate bodies that were scattered throughout the cytoplasm. These findings suggest that the truncated DRPLA proteins containing expanded polyQ stretches unfold and form small aggregate bodies in the cell periphery. These aggregates move on MTs to the MTOC, where they remain as distinct 'aggresomes'. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(02)00162-3

Time course of polyglutamine aggregate body formation and cell death: Enhanced growth in nucleus and an interval for cell death 査読

Toyoshima, I, M Sugawara, K Kato, C Wada, T Shimohata, R Koide, O Onodera, S Tsuji

JOURNAL OF NEUROSCIENCE RESEARCH 68 ( 4 ) 442 - 448 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY-LISS

Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral-pallidoluysian atrophy and related neurodegenerative disorders, although the relationship between aggregate body formation and cell death is not clear. We analyzed the kinetics of polyQ aggregate formation and the time intervals for cell death, tracking individual cells using fluorescence video microscopy, for the first time. Expanded polyQ tracts of atrophin-1 with or without nuclear localization signal (NLS) labeled with green fluorescent protein (GFP) were constructed, Q57NLS/GFP and Q56/GFP, respectively. All of the Q57NLS/GFP aggregate bodies were in nuclei, and all of the Q56/GFP aggregate bodies were in cytoplasm. Aggregates of Q56/GFP were larger than those of Q57NLS/ GFP. Surprisingly, a kinetic analysis showed that the latter grew 5.37 times faster than the former. The time interval between transfection and cell death was shorter in Q57NLS/GFP, but the time between the end of the rapid growing phase of aggregation and the start of the cell death process did not show a significant difference. Aggregate growth was confirmed to correspond to the accumulated free polyQ by the time of starting aggregation. These findings suggest that aggregate body formation induced by expanded polyQ stretches is a self-limiting process and is enhanced by factor(s) in nuclei, whereas it is not tightly bound to the cell death process. (C) 2002 Wiley-Liss,

DOI： 10.1002/jnr.10233

Epidemiology of X-linked adrenoleukodystrophy in Japan 査読

Y Takemoto, Y Suzuki, A Tamakoshi, O Onodera, S Tsuji, T Hashimoto, N Shimozawa, T Orii, N Kondo

JOURNAL OF HUMAN GENETICS 47 ( 11 ) 590 - 593 2002年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER-VERLAG TOKYO

To clarify the epidemiology of X-linked adrenoleukodystrophy (ALD) in Japan, we performed a questionnaire survey. Two hundred eighty-six patients, including 154 from internal medicine, 100 from pediatrics, 21 from psychiatry, and I I from other hospitals, were reported to have ALD between 1990 and 1999. The data on 154 patients revealed the phenotypic distribution to be as follows: childhood cerebral form (29.9%), adrenomyeloneuropathy (25.3%), adult cerebral form (21.4%), adolescent form (9.1%), olivo-ponto-cerebellar form (8.4%), presymptomatic form (4.5%), and symptomatic female patient (1.3%). The adult cerebral form and olivo-ponto-cerebellar form were more common in Japan than in North America and Europe. The incidence of X-linked ALD in Japan was estimated to be between 1: 30 000 and 1: 50 000 boys, similar to previous reports. About half of the patients with adrenomyeloneuropathy and the olivo-ponto-cerebellar phenotype developed cerebral involvement with a mean interval of 8.2 and 2.2 years after ALD onset, respectively. The family histories revealed that brothers and first cousins tended to show similar phenotypes, whereas nephews tended to develop symptoms earlier than uncles. These data will help in understanding the natural history of X-linked ALD.

DOI： 10.1007/s100380200090

Paraneoplastic striatal encephalitis 査読

T Oguma, H Kobayashi, S Katada, O Onodera, K Tanaka, S Tsuji, T Uno, T Ishida, H Kagamu, F Gejyo, M Motomura

NEUROLOGY 57 ( 12 ) 2326 - 2326 2001年12月

Amino acid sequences flanking polyglutamine stretches influence their potential for aggregate formation 査読

K Nozaki, O Onodera, H Takano, S Tsuji

NEUROREPORT 12 ( 15 ) 3357 - 3364 2001年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Expanded polyglutamine stretches have been shown to form aggregates and to be toxic to cells. In this study, we hypothesized that amino acid sequences flanking the polyglutamine stretches influence the aggregate formation potential of these stretches. Green fluorescent protein (GFP) fusion proteins containing glutamine repeats of various lengths and a fixed number of flanking amino acids of ataxin-2, huntingtin, clentatorubral-pallidoluysian atrophy protein (DRPLAP) or ataxin-3 were transiently expressed in COS-7 cells. The aggregate formation potential of ataxin-2 and DRPLAP increased in a CAG-repeat-length-dependent manner, with a threshold between 34 and 36. Truncated ataxin-2-Q56-GFP and truncated huntingtin-Q56-GFP showed a significantly higher aggregate formation potential than truncated DRPLAP-Q56-GFP or truncated ataxin-3-Q56-GFP. These results are in agreement with the clinical observation that ages of disease onset in patients with spinocerebellar ataxia type 2 or Huntington's disease are lower than those in patients with DRPLA or Machado-Joseph disease having expanded CAG repeats of the same length. Furthermore, mutagenesis of the flanking sequence of ataxin-2 markedly reduced its aggregate formation potential. These results indicate that the amino acid sequences flanking the polyglutamine stretches significantly influence their aggregate formation potential. NeuroReport 12:3357-3364 (C) 2001 Lippincott Williams & Wilkins.