Abstract
Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in Nrf2 gene promoter: −653 A/G, −651 G/A, and −617 C/A and evaluated, in a subset (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers. Nrf2 polymorphisms were not different among patients and controls. Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance and Nrf2 polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the −653 A/G, −651 G/A, and −617 C/A Nrf2 SNPs in ALS patients.
Highlights
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive degeneration of the anterior horn cells of the spinal cord [1] and cortical motor neurons [2]
Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS)
The frequency of the variant allele G in −653 A/G polymorphism is lightly higher in patients than controls, but this difference was not statistically significant
Summary
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by progressive degeneration of the anterior horn cells of the spinal cord [1] and cortical motor neurons [2]. SALS and fALS are clinically indistinguishable and good evidence suggests that they basically share a common pathogenic mechanism that includes oxidative stress, excitotoxicity, and mitochondrial dysfunction [3, 4]. Mitochondria play central roles in cell’s bioenergetics and apoptosis, and mitochondrial dysfunction appears to be involved in the pathogenesis of several neurodegenerative diseases, including motor neuron diseases [3]. Multiple reports of oxidative damage in the spinal cord and in motor neurons of the motor cortex in postmortem tissues of both sALS and fALS cases are published revised in [7]. Among the mechanisms which can be involved in this contest, gene expression profiling of motor neurons that express the mutated form of SOD1 shows a reduced regulation of some genes involved in antioxidant response, including
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