Mutant Cu/Zn-Superoxide Dismutase Induced Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Koistinaho, Jari; Goldsteins, Gundars

doi:10.5772/32751

Cited by 2 publications

(1 citation statement)

References 87 publications

(92 reference statements)

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“…The SOD1 activity in the mitochondrial inter-membrane space is a relevant therapeutic target for ALS and other neurodegenerative diseases involving mitochondrial pathogenesis has been confirmed [78].…”

Section: More Update On Alsmentioning

confidence: 96%

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

Foyaca-Sibat¹,

Valdés²

2016

Update on Amyotrophic Lateral Sclerosis

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Section: More Update On Alsmentioning

confidence: 96%

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

Foyaca-Sibat¹,

Valdés²

2016

Update on Amyotrophic Lateral Sclerosis

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Gly482Ser PGC-1α Gene Polymorphism and Exercise-Related Oxidative Stress in Amyotrophic Lateral Sclerosis Patients

Pasquinelli

Chico

Pasquali

et al. 2016

Front. Cell. Neurosci.

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The role of exercise in Amyotrophic lateral sclerosis (ALS) pathogenesis is controversial and unclear. Exercise induces a pleiotropic adaptive response in skeletal muscle, largely through the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that regulates mitochondrial biogenesis and antioxidant defense mechanisms. It has been suggested that a Gly482Ser substitution in PGC-1α has functional relevance in human disorders and in athletic performance. To test this hypothesis, we examined the genotype distribution of PGC-1α Gly482Ser (1444 G > A) in ALS patients to evaluate whether or not the minor serine-encoding allele 482Ser is involved in oxidative stress responses during physical exercise. We genotyped 197 sporadic ALS patients and 197 healthy controls in order to detect differences in allelic frequencies and genotype distribution between the two groups. A total of 74 ALS patients and 65 controls were then comparatively assessed for plasmatic levels of the oxidative stress biomarkers, advanced oxidation protein products, ferric reducing ability and thiol groups. In addition a subgroup of 35 ALS patients were also assessed for total SOD and catalase plasmatic activity. Finally in 28 ALS patients we evaluated the plasmatic curve of the oxidative stress biomarkers and lactate during an incremental exercise test. No significant differences were observed in the genotype distribution and allelic frequency in ALS patients compared to the controls. We found significant increased advanced oxidation protein products (p < 0.001) and significant decreased ferric reducing ability (p < 0.001) and thiol groups (p < 0.001) in ALS patients compared to controls. When comparing different genotypes of PGC-1α, no relation between Gly482Ser polymorphism and oxidative stress biomarker levels was detected in resting conditions. On the other hand, when considering exercise performance, lactate levels were significantly higher (between p < 0.01 and p < 0.001) and greater protein oxidative products were found in AA (Ser482Ser) compared to GG (Gly482Gly) and GA (Gly482Ser) ALS patients. Our findings highlight the importance and confirm the involvement of oxidative stress in ALS pathogenesis. Although not associated with 1444 G > A SNP, ALS patients with Gly482Ser allelic variant show increased exercise-related oxidative stress. This thus highlights the possible role of this antioxidant defense transcriptional coactivator in ALS.

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Mutant Cu/Zn-Superoxide Dismutase Induced Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis

Cited by 2 publications

References 87 publications

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

Introductory Chapter: Introduction to Update in Amyotrophic Lateral Sclerosis and Review of this Condition in Sportsmen

Gly482Ser PGC-1α Gene Polymorphism and Exercise-Related Oxidative Stress in Amyotrophic Lateral Sclerosis Patients

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