Activities of mitochondrial complexes correlate with nNOS amount in muscle from ALS patients

The pathogenesis of amyotrophic lateral sclerosis (ALS) is poorly understood. Increased levels of free radicals derived from nitric oxide (NO), the product of nitric oxide synthase (NOS), may damage mitochondrial function leading to motor neurone death. Previous studies demonstrated a specific impairment of mitochondrial function in skeletal muscle of ALS patients. In order to verify a pathogenetic relationship between neuronal NOS (nNOS) and mitochondrial function, we studied nNOS expression by Western blot and mitochondrial enzyme activity by spectrophotometric assays in muscle biopsies of 16 sporadic ALS patients and 16 controls subjects. We observed a reduced activity of respiratory chain complexes with mitochondrial encoded subunits and a lower nNOS amount in ALS muscles. There was a direct correlation between levels of nNOS and values of mitochondrial enzymes function. In ALS muscles we found normal levels of manganese superoxide dismutase (SOD2) that is assumed as related to mitochondrial DNA abnormalities. Our data suggest a beneficial role for NO to mitochondrial function and lead to the hypothesis of a common oxidative damage in motor neurones and skeletal muscle in sporadic ALS patients.