球脊髄性筋萎縮症
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English Journal
- Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.
- Turner BJ1, Alfazema N2, Sheean RK3, Sleigh JN4, Davies KE2, Horne MK3, Talbot K5.Author information 1Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Victoria, Australia; Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia. Electronic address: bradley.turner@florey.edu.au.2MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.3Florey Institute of Neuroscience & Mental Health, University of Melbourne, Parkville, Victoria, Australia; Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia.4MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.5MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK. Electronic address: kevin.talbot@ndcn.ox.ac.uk.AbstractSpinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS.
- Neurobiology of aging.Neurobiol Aging.2014 Apr;35(4):906-15. doi: 10.1016/j.neurobiolaging.2013.09.030. Epub 2013 Oct 24.
- Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phen
- PMID 24210254
- Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA).
- Hensel N1, Stockbrügger I2, Rademacher S1, Broughton N2, Brinkmann H2, Grothe C1, Claus P3.Author information 1Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany.2Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany.3Institute of Neuroanatomy, Hannover Medical School, 30625 Hannover, Germany; Center for Systems Neuroscience (ZSN), 30559 Hannover, Germany; Niedersachsen Research Network on Neuroinfection (N-RENNT), Germany. Electronic address: claus.peter@mh-hannover.de.AbstractRho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a bilateral ROCK-ERK information flow in neurons. This process is shifted towards an unidirectional crosstalk in a model of the neurodegenerative disease Spinal Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations. As both pathways are of therapeutic relevance for SMA, our results argue for a combinatorial ROCK/ERK-targeting as a future treatment strategy.
- Cellular signalling.Cell Signal.2014 Mar;26(3):540-8. doi: 10.1016/j.cellsig.2013.11.027. Epub 2013 Dec 3.
- Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here
- PMID 24316236
- Novel Dynein DYNC1H1 Neck and Motor Domain Mutations Link Distal Spinal Muscular Atrophy and Abnormal Cortical Development.
- Fiorillo C, Moro F, Yi J, Weil S, Brisca G, Astrea G, Severino M, Romano A, Battini R, Rossi A, Minetti C, Bruno C, Santorelli FM, Vallee R.Author information Neuromuscular and Molecular Medicine Unit, Department of Developmental Neuroscience, IRCCS Stella Maris, Pisa, Italy.AbstractDYNC1H1 encodes the heavy chain of cytoplasmic dynein 1, a motor protein complex implicated in retrograde axonal transport, neuronal migration, and other intracellular motility functions. Mutations in DYNC1H1 have been described in autosomal-dominant Charcot-Marie-Tooth type 2 and in families with distal spinal muscular atrophy (SMA) predominantly affecting the legs (SMA-LED). Recently, defects of cytoplasmic dynein 1 were also associated with a form of mental retardation and neuronal migration disorders. Here, we describe two unrelated patients presenting a combined phenotype of congenital motor neuron disease associated with focal areas of cortical malformation. In each patient, we identified a novel de novo mutation in DYNC1H1: c.3581A>G (p.Gln1194Arg) in one case and c.9142G>A (p.Glu3048Lys) in the other. The mutations lie in different domains of the dynein heavy chain, and are deleterious to protein function as indicated by assays for Golgi recovery after nocodazole washout in patient fibroblasts. Our results expand the set of pathological mutations in DYNC1H1, reinforce the role of cytoplasmic dynein in disorders of neuronal migration, and provide evidence for a syndrome including spinal nerve degeneration and brain developmental problems.
- Human mutation.Hum Mutat.2014 Mar;35(3):298-302. doi: 10.1002/humu.22491. Epub 2014 Jan 3.
- DYNC1H1 encodes the heavy chain of cytoplasmic dynein 1, a motor protein complex implicated in retrograde axonal transport, neuronal migration, and other intracellular motility functions. Mutations in DYNC1H1 have been described in autosomal-dominant Charcot-Marie-Tooth type 2 and in families with d
- PMID 24307404
Japanese Journal
- Familial bulbospinal neuronopathy with optic atrophy : a distinct entity
- X-linked Recessive Bulbospinal Neuronopathy (SBMA)
- Sobue Gen
- Nagoya journal of medical science 58(3/4), 95-106, 1995-12
- NAID 110000023119
- Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene
Related Links
- 96 Gen Sobue the molecular mechanism of the pathogenic role of the increased CAG repeats in the respon sible gene of each disease in unknown. Furthermore, the normal functions of the deduced pro teins encoded at the loci for ...
- Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology. 1968 Jul; 18 (7):671–680. [PubMed] La Spada AR, Wilson EM, Lubahn DB, Harding AE ...
Related Pictures
![Muscular Atrophy; Bulbospinal Neuronopathy](https://1mg.info/0/d/p/2359.jpg)
![Muscular Atrophy; Bulbospinal Neuronopathy](https://1mg.info/0/d/p/2360.jpg)
![Muscular Atrophy; Bulbospinal Neuronopathy](https://1mg.info/0/d/p/2361.jpg)
![Spinal muscular atrophy (SMA) type II with](https://1mg.info/0/d/p/2362.jpg)
![Spinal Muscular Atrophy ,](https://1mg.info/0/d/p/2363.jpg)
★リンクテーブル★
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- 英
- spinobulbar muscular atrophy SBMA , spinal and bulbar muscular atrophy, bulbospinal muscular atrophy BSMA
- 同
- 球脊髄ニューロン症 bulbospinal neuronopathy、ケネディ・オルター・スン症候群 Kennedy-Alter-Sung症候群 Kennedy-Alter-Sung syndrome Kennedy-Alter-Sung disease、ケネディ病 Kennedy disease
- 関
- 運動ニューロン疾患、脊髄性筋萎縮症、トリプレットリピート病、脊髄性進行性筋萎縮症
概念
- 成人期に発症する緩徐進行性の筋萎縮症で、下位運動ニューロンを冒す。
- 運動ニューロン疾患でありながら、近位筋優位に障害される。
疫学
病因
- X染色体に座乗するアンドロゲン受容体の第1エキソンに存在するCAGリピートが延長していることによる。
遺伝形式
徴候
アンドロゲン受容体の異常に基づく
- 性腺機能異常(女性化乳房、インポテンツ、性腺萎縮、無精子症)
筋萎縮に随伴
- 球麻痺(嚥下障害、構音障害)
- 筋萎縮(顔面筋・舌筋萎縮)
- 筋線維束攣縮
検査
- CK:軽度上昇
- 筋電図:
- 遺伝子検査:(CKや筋電図で十分であるが)非定型例や保因者の診断に有用
診断
治療
予後
参考
- http://grj.umin.jp/grj/kennedy.htm
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遠位型脊髄性筋萎縮症、遠位型脊髄性筋萎縮
- 関
- bulbospinal neuronopathy、Kennedy syndrome、progressive muscular atrophy、spinal muscular atrophy
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進行性筋萎縮症、進行性筋萎縮
- 関
- bulbospinal neuronopathy、distal spinal muscular atrophy、Kennedy syndrome、spinal muscular atrophy
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