Visualization of defective mitochondrial function in skeletal muscle fibers of patients with sporadic amyotrophic lateral sclerosis

Vielhaber, Stefan; Winkler, Kirstin; Kirches, Elmar; Kunz, Dagmar; Büchner, Maren; Feistner, Helmut; Elger, Christian E.; Ludolph, Albert C.; Riepe, Matthias W.; Kunz, Wolfram S.

doi:10.1016/s0022-510x(99)00236-1

Cited by 106 publications

(75 citation statements)

References 24 publications

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“…We and others had previously shown mitochondrial dysfunction accompanied by ATP depletion and uncoupling protein 3 upregulation in skeletal muscle of mSOD1 mice (16) and ALS patients (28)(29)(30)(31). It is thus probable that this mitochondrial impairment could underlie the increased energy needs of skeletal muscle, as reflected by the increased rates of glucose uptake (6) and TG clearance shown here.…”

Section: Discussionsupporting

confidence: 57%

Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis

Fergani

Oudart

Aguilar

et al. 2007

Journal of Lipid Research

108

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Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease, causing motor neuron degeneration, muscle atrophy, paralysis, and death. Despite this degenerative process, a stable hypermetabolic state has been observed in a large subset of patients. Mice expressing a mutant form of Cu/Zn-superoxide dismutase (mSOD1 mice) constitute an animal model of ALS that, like patients, exhibits unexpectedly increased energy expenditure. Counterbalancing for this increase with a high-fat diet extends lifespan and prevents motor neuron loss. Here, we investigated whether lipid metabolism is defective in this animal model. Hepatic lipid metabolism was roughly normal, whereas gastrointestinal absorption of lipids as well as peripheral clearance of triglyceride-rich lipoproteins were markedly increased, leading to decreased postprandial lipidemia. This defect was corrected by the high-fat regimen that typically induces neuroprotection in these animals. Together, our findings show that energy metabolism in mSOD1 mice shifts toward an increase in the peripheral use of lipids. This metabolic shift probably accounts for the protective effect of dietary lipids in this model.-Fergani, A

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Section: Discussionsupporting

confidence: 57%

Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis

Fergani

Oudart

Aguilar

et al. 2007

Journal of Lipid Research

108

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“…In addition, several studies conducted on muscle biopsies obtained from patients pointed to mitochondrial dysfunction, as revealed by biochemical abnormalities (22,106,107,123,127), alterations of mitochondrial DNA (2, 122) and, in some cases, ultrastructural modifications (16). Contrasting with these observations, other studies showed that mitochondrial damage was only mild (1, 37, 62, 102) but increased with disease progression (36).…”

Section: Oxidative Stress and Mitochondrial Dysfunction Characterize mentioning

confidence: 99%

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

et al. 2016

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Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets.

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“…1). In addition there is strong evidence that complex I inhibition, through accumulated damage caused by reactive oxygen and nitrogen species and by the binding of environmental toxins, has a role in the development of the more prevalent neurodegenerative disorders including Parkinson's disease (2-4), Alzheimer's disease (5), Huntington's disease (6), amyotrophic lateral sclerosis (7,8), Down's syndrome (5), schizophrenia (9), and even the process of aging itself (10).…”

mentioning

confidence: 99%

The Subunit Composition of the Human NADH Dehydrogenase Obtained by Rapid One-step Immunopurification

Murray

Zhang²,

Taylor³

et al. 2003

Journal of Biological Chemistry

100

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Visualization of defective mitochondrial function in skeletal muscle fibers of patients with sporadic amyotrophic lateral sclerosis

Cited by 106 publications

References 24 publications

Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis

Increased peripheral lipid clearance in an animal model of amyotrophic lateral sclerosis

The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis

The Subunit Composition of the Human NADH Dehydrogenase Obtained by Rapid One-step Immunopurification

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