Progress in the pathogenesis of amyotrophic lateral sclerosis.

被引：53

作者：

Shaw C.E. ^{[1
]}

Al-Chalabi A. ^{[2
]}

Leigh N. ^{[2
]}

机构：

[1] Department of Neurology, Guy’s, King’s, and St. Thomas’ School of Medicine, Institute of Psychiatry, London SE5 8AS, De Crespigny Park

[2] Department of Medical and Molecular Genetics, Guy’s, King’s, and St. Thomas’ School of Medicine, London

来源：

Current Neurology and Neuroscience Reports | 2001年 / 1卷 / 1期

关键词：

Amyotrophic Lateral Sclerosis; Motor Neuron; Motor Neuron Disease; Sporadic Amyotrophic Lateral Sclerosis; Familial Amyotrophic Lateral Sclerosis;

D O I：

10.1007/s11910-001-0078-7

中图分类号：

学科分类号：

摘要：

This decade has seen the discovery of one cause for amyotrophic lateral sclerosis (ALS)--mutations in the copper/zinc superoxide dismutase (SOD1) gene. Mutant SOD1 has provided an invaluable tool for transgenic and cellular experiments designed to elicit the biochemical pathways that are disturbed in ALS. We highlight recent advances in ALS research, including diagnostic issues, new loci for ALS genes, and progress in understanding the toxicity of mutant SOD1. The evidence for persistant viral infection, glutamate-mediated excitotoxicity, oxidative stress, altered neurofilament and peripherin expression, disrupted axonal transport, neurotrophin deficiency, and mitochondrial dysfunction are critically reviewed. As yet, no consensus has been achieved on the pathways that lead to selective neuronal death, and the underlying causes are still unknown in the vast majority of patients. Further clues about genetic susceptibility and environmental triggers are urgently needed so that more effective treatments for ALS can be developed, with the ultimate goal being prevention.

引用

页码：69 / 76

页数：7

共 67 条

[11]

Rosen DR, Siddique T, Patterson D, Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis, Nature, 362, pp. 59-62, (1993)

[12]

Shaw CE, Enayat ZE, Chioza BA, Mutations in all five exons of SOD-1 may cause ALS, Ann Neurol, 43, pp. 390-394, (1998)

[13]

Shaw CE, Enayat ZE, Powell JF, Familial amyotrophic lateral sclerosis. Molecular pathology of a patient with a SOD1 mutation, Neurology, 49, pp. 1612-1616, (1997)

[14]

Ince PG, Tomkins J, Slade JY, Amyotrophic lateral sclerosis associated with genetic abnormalities in the gene encoding Cu/Zn superoxide dismutase: molecular pathology of five new cases, and comparison with previous reports and 73 sporadic cases of ALS, J Neuropath Exp Neurol, 57, pp. 895-904, (1998)

[15]

Andersen PM, Forsgren L, Binzer M, Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and genealogical study of 36 patients, Brain, 119, pp. 1153-1172, (1996)

[16]

Ratovitski T, Corson LB, Strain J, Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds, Hum Mol Genet, 8, pp. 1451-1460, (1999)

[17]

Neilson S, Robinson I, Nymoen EH, Longitudinal analysis of amyotrophic lateral sclerosis mortality in Norway, 1966–1989: evidence for a susceptible subpopulation, J Neurol Sci, 122, pp. 148-154, (1994)

[18]

Gurney ME, Pu H, Chiu AY, Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation, Science, 264, pp. 1772-1775, (1994)

[19]

Brown RH, Superoxide dismutase and familial amyotrophic lateral sclerosis: New insights into mechanisms and treatments, Ann Neurol, 39, pp. 145-146, (1996)

[20]

Durham HD, Roy J, Dong L, Figlewicz DA, Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS, J Neuropathol Exp Neurol, 56, pp. 523-530, (1997)

← 1 2 3 4 5 6 7 →