Amyotrophic lateral sclerosis linked to a novel SOD1 mutation with muscle mitochondrial dysfunction

被引：31

作者：

Corti, Stefania ^{[1
,2
]}

Donadoni, Chiara ^{[1
]}

Ronchi, Dario ^{[1
]}

Bordoni, Andreina ^{[1
]}

Fortunato, Francesco ^{[1
]}

Santoro, Domenico ^{[1
]}

Del Bo, Roberto ^{[1
]}

Lucchini, Valeria ^{[1
]}

Crugnola, Veronica ^{[1
]}

Papadimitriou, Dimitra ^{[1
]}

Salani, Sabrina ^{[1
]}

Moggio, Maurizio ^{[1
]}

Bresolin, Nereo ^{[1
,2
,3
]}

Comi, Giacomo P. ^{[1
,2
]}

机构：

[1] Univ Milan, Dept Neurol Sci, IRCCS Fdn Osped Maggiore Policlin, Dino Ferrari Ctr, I-20122 Milan, Italy

[2] Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy

[3] IRCCS Eugenio Medea, Lecce, Italy

来源：

JOURNAL OF THE NEUROLOGICAL SCIENCES | 2009年 / 276卷 / 1-2期

关键词：

Amyotrophic lateral sclerosis; Motor neuron; Mitochondria; SOD1; SUPEROXIDE-DISMUTASE GENE; SKELETAL-MUSCLE; FAMILIAL ALS; FIBERS; MODELS; INJURY; MICE;

D O I：

10.1016/j.jns.2008.09.030

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

100204 [神经病学];

摘要：

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative motor neuron disorder. Mutations in Cu,Zn superoxide dismutase (SOD]) cause approximately 20% of familial ALS. One of the possible mechanisms whereby they induce disease is mitochondrial dysfunction in motor neurons. Here we describe a patient with ALS and muscle mitochondrial oxidative defect associated with a novel SOD1 Mutation. Direct sequencing of SOD1 gene revealed a heterozygous mutation in codon 22 substituting a highly conserved amino acid, from glutamine to arginine (Q22R). Muscle biopsy showed a neurogenic pattern associated with cytochrome c oxidase (COX) deficiency in several muscle fibers. Western blot analysis demonstrated a reduction in SOD1 content in the cytoplasmic and mitochondrial fractions. These results suggest that a minute quantity of mutant SOD1 protein contributes to a mitochondrial toxicity also in muscle tissue. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：170 / 174

页数：5

共 32 条

[1]

Wild-type superoxide dismutase acquires binding and toxic properties of ALS-linked mutant forms through oxidation [J].