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1. 脊髄および後根神経節に影響を与える腫瘍随伴性症候群 paraneoplastic syndromes affecting the spinal cord and dorsal root ganglia
2. 感覚消失患者へのアプローチ approach to the patient with sensory loss
3. 進行性多巣性白質脳症：疫学、臨床症状、および診断 progressive multifocal leukoencephalopathy epidemiology clinical manifestations and diagnosis
4. 腫瘍随伴性および自己免疫性脳炎 paraneoplastic and autoimmune encephalitis
5. 末梢神経と筋肉に影響を与える腫瘍随伴性症候群 paraneoplastic syndromes affecting peripheral nerve and muscle

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