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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
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of special interest. A synthesis of various current ideas on the pathogenesis of ALS. The author discusses links among the various proposed mechanisms for chronic motor neuron degeneration.
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of special interest Brown RH Jr. Amyotrophic lateral sclerosis recent insights from genetics and transgenic mice. Cell. 80:1995;687-692 A synthesis of various current ideas on the pathogenesis of ALS. The author discusses links among the various proposed mechanisms for chronic motor neuron degeneration.
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of special interest Rothstein JD. Pathogenesis of ALS: the excitotoxicity hypothesis. Neurology. 1996; A review of the role of excitotoxicity in the pathogenesis of ALS.
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Rothstein, J.D.1
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Immunoglobulins from animal models of motor neuron disease and from amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction
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Appel SH, Engelhardt JI, Garcia J, Stefani E. Immunoglobulins from animal models of motor neuron disease and from amyotrophic lateral sclerosis patients passively transfer physiological abnormalities to the neuromuscular junction. Proc Natl Acad Sci USA. 88:1991;647-651.
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Appel, S.H.1
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Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis
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Smith RG, Hamilton S, Hofmann F, Schneider T, Nastainczyk WCS, Birnbaumer L, Stefani E, Appel SH. Serum antibodies to L-type calcium channels in patients with amyotrophic lateral sclerosis. N Engl J Med. 327:1992;1721-1728.
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Rothstein JD, Martin LJ, Kuncl RW. Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis. N Engl J Med. 326:1992;1464-1468.
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Rothstein, J.D.1
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[3H]D-aspartate binding sites in the normal human spinal cord and changes in motor neuron disease: A quantitative autoradiographic study
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Shaw PJ, Chinnery RM, Ince PG. [3H]D-aspartate binding sites in the normal human spinal cord and changes in motor neuron disease: a quantitative autoradiographic study. Brain Res. 655:1994;195-201.
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Shaw, P.J.1
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Antisense knockout of glutamate transporters reveals a predominant role for astroglial glutamate transport in excitotoxicity and clearance of extracellular glutamate
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of special interest. This study, largely designed to evaluate the basic physiology of glutamate transporter subtypes, demonstrates that a loss of astroglial, especially GLT-1 (see [19]), glutamate transporters, can lead to neurotoxicity and elevated extracellular glutamate levels.
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of special interest Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke J, Welty DF. Antisense knockout of glutamate transporters reveals a predominant role for astroglial glutamate transport in excitotoxicity and clearance of extracellular glutamate. Neuron. 16:1996;675-686 This study, largely designed to evaluate the basic physiology of glutamate transporter subtypes, demonstrates that a loss of astroglial, especially GLT-1 (see [19]), glutamate transporters, can lead to neurotoxicity and elevated extracellular glutamate levels.
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Neuron
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Rothstein, J.D.1
Dykes-Hoberg, M.2
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Bristol, L.A.4
Jin, L.5
Kuncl, R.W.6
Kanai, Y.7
Hediger, M.A.8
Wang, Y.9
Schielke, J.10
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Shaw PJ, Ince PG, Falkous G, Mantle D. Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol. 38:1995;691-695.
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Shaw, P.J.1
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Bowling AC, Schulz JB, Brown RH Jr, Beal MF. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem. 61:1993;2322-2325.
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Neuronal growth and death: Order and disorder in the axoplasm
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of special interest. The author provides a concise review of neurofilament biology and how neurofilament abnormalities could contribute to motor neuron disease.
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of special interest Cleveland DW. Neuronal growth and death: order and disorder in the axoplasm. Cell. 84:1996;663-666 The author provides a concise review of neurofilament biology and how neurofilament abnormalities could contribute to motor neuron disease.
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Cell
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Cleveland, D.W.1
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19
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0029030610
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Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis
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of special interest. Some sporadic ALS patients appear to have a loss of glutamate transport activity in neuropathologically affected brain regions [12]. These changes were not seen in disease controls, including Alzheimer's and Huntington's disease patients. This study demonstrates that the functional defects in glutamate transport demonstrated in [12] are probably attributable to a selective loss of the astroglial glutamate transporter GLT-1 and not to the other astroglial transporter GLAST or the neuronal glutamate transporter EAAC1.
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of special interest Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol. 38:1995;73-84 Some sporadic ALS patients appear to have a loss of glutamate transport activity in neuropathologically affected brain regions [12]. These changes were not seen in disease controls, including Alzheimer's and Huntington's disease patients. This study demonstrates that the functional defects in glutamate transport demonstrated in [12] are probably attributable to a selective loss of the astroglial glutamate transporter GLT-1 and not to the other astroglial transporter GLAST or the neuronal glutamate transporter EAAC1.
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Ann Neurol
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Rothstein, J.D.1
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Rothstein JD, Tsai G, Kuncl RW, Clawson L, Cornblath DR, Drachman DB, Pestronk A, Stauch BL, Coyle JT. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol. 28:1990;18-25.
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CSF and plasma amino acid levels in motor neuron disease - Elevation of CSF glutamate in a subset of patients
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Shaw PJ, Forest V, Ince PG, Richardson JP, Wastell HJ. CSF and plasma amino acid levels in motor neuron disease - elevation of CSF glutamate in a subset of patients. Neurodegeneration. 4:1995;209-216.
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An abnormal mRNA leads in downregulation of glutamate transporter EAAT2 (GLT-1) expression in familial amyotrophic lateral sclerosis
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Lin G, Bristol LA, Rothstein JD. An abnormal mRNA leads in downregulation of glutamate transporter EAAT2 (GLT-1) expression in familial amyotrophic lateral sclerosis. Ann Neurol. 40:1996;540-541.
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0030050727
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Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis
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of outstanding interest. The first clinical trials of SOD1 transgenic mice. Anti-glutamate (riluzole and gabapentin) drugs and the antioxidant vitamin E were studied and found to alter the course of the disease in these mice. Notably, the antioxidants delayed disease onset but not overall survival of the mice,; whereas the antiglutamates did not alter disease onset, but slightly increased survival. This paper suggests that both initiating and propagating processes may occur in ALS.
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of outstanding interest Gurney ME, Cuttings FB, Zhai P, Doble A, Taylor CP, Andrus PK, Hall ED. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann Neurol. 39:1996;147-157 The first clinical trials of SOD1 transgenic mice. Anti-glutamate (riluzole and gabapentin) drugs and the antioxidant vitamin E were studied and found to alter the course of the disease in these mice. Notably, the antioxidants delayed disease onset but not overall survival of the mice,; whereas the antiglutamates did not alter disease onset, but slightly increased survival. This paper suggests that both initiating and propagating processes may occur in ALS.
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Ann Neurol
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Gurney, M.E.1
Cuttings, F.B.2
Zhai, P.3
Doble, A.4
Taylor, C.P.5
Andrus, P.K.6
Hall, E.D.7
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24
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0029053881
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An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria
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of outstanding interest. A detailed study of transgenic mice carrying a different SOD1 mutation, G37R, from the one studied by Gurney et al [23]. The authors provide a detailed neuropathological and biochemical evaluation of the progression of the disease in these mice. Similar to this study by Gurney et al. [23], this study confirms the selective motor neuron degeneration associated with a SOD1 mutation. The G37R mutation appears to cause a vacuolar-type degeneration. Furthermore, the authors suggest that the toxicity associated with the SOD1 mutation confirms a gain-of-adverse property, rather than a simple loss of function.
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of outstanding interest Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron. 14:1995;1105-1116 A detailed study of transgenic mice carrying a different SOD1 mutation, G37R, from the one studied by Gurney et al [23]. The authors provide a detailed neuropathological and biochemical evaluation of the progression of the disease in these mice. Similar to this study by Gurney et al. [23], this study confirms the selective motor neuron degeneration associated with a SOD1 mutation. The G37R mutation appears to cause a vacuolar-type degeneration. Furthermore, the authors suggest that the toxicity associated with the SOD1 mutation confirms a gain-of-adverse property, rather than a simple loss of function.
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Neuron
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Wong, P.C.1
Pardo, C.A.2
Borchelt, D.R.3
Lee, M.K.4
Copeland, N.G.5
Jenkins, N.A.6
Sisodia, S.S.7
Cleveland, D.W.8
Price, D.L.9
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25
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A mutant neurofilament subunit causes massive, selective motor neuron death: Implications for the pathogenesis of human motor neuron disease
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Lee MK, Marszalek JR, Cleveland DW. A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron. 13:1994;975-988.
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Lee, M.K.1
Marszalek, J.R.2
Cleveland, D.W.3
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Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease
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Xu Z, Cork LC, Griffin JW, Cleveland DW. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell. 73:1993;23-33.
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Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons
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of special interest. The first detailed study of the distribution of SOD1 in the CNS. The authors demonstrate the relatively ubiquitous localization of SOD1 to neurons and glia.
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of special interest Pardo CA, Xu Z, Borchelt DR, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. Proc Natl Acad Sci USA. 92:1995;954-958 The first detailed study of the distribution of SOD1 in the CNS. The authors demonstrate the relatively ubiquitous localization of SOD1 to neurons and glia.
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Proc Natl Acad Sci USA
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Pardo, C.A.1
Xu, Z.2
Borchelt, D.R.3
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Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng H-X, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 264:1994;1772-1775.
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Gurney, M.E.1
Pu, H.2
Chiu, A.Y.3
Dal Canto, M.C.4
Polchow, C.Y.5
Alexander, D.D.6
Caliendo, J.7
Hentati, A.8
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Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. N Engl J Med. 330:1994;585-591.
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Dose-ranging study of riluzole in amyotrophic lateral sclerosis
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of outstanding interest. In this dose-ranging follow-up study (see [39]), the beneficial effect of riluzole in ALS was confirmed. In spite of this success, perplexing questions still remain. If patients lived longer, why did the drug not alter their decline in motor strength and pulmonary function?
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of outstanding interest Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V. Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet. 347:1996;1425-1431 In this dose-ranging follow-up study (see [39]), the beneficial effect of riluzole in ALS was confirmed. In spite of this success, perplexing questions still remain. If patients lived longer, why did the drug not alter their decline in motor strength and pulmonary function?
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Lancet
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Lacomblez, L.1
Bensimon, G.2
Leigh, P.N.3
Guillet, P.4
Meininger, V.5
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Przedborski S, Donaldson D, Janowec M, Kish SJ, Guttman M, Rosoklija G, Hays AP. Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis. Ann Neurol. 39:1996;158-165.
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Ann Neurol
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Przedborski, S.1
Donaldson, D.2
Janowec, M.3
Kish, S.J.4
Guttman, M.5
Rosoklija, G.6
Hays, A.P.7
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Rothstein JD, Bristol LA, Hosler B, Brown RH Jr, Kuncl RW. Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Natl Acad Sci USA. 91:1994;4155-4159.
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43
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0029113872
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Neuroprotective strategies in a model of chronic glutamate-mediated motor neuron toxicity
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