Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause approximately 20% of cases of familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism of mutant SOD-induced neuronal degeneration by expressing wild-type and mutant SODs in neuronal cells by means of infection with replication-deficient recombinant adenoviruses. Expression of two FALS-related mutant SODs (A4V and V...

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurological disorder with higher selectivity in the degeneration of the upper and lower motor neurons, which leads to progres‐ sive paralysis of voluntary muscles. Although most cases fall under sporadic ALS (sALS), 10% of cases are inherited and known as familial ALS (fALS). The etiology of most ALS cases remains unknown, but mutations of ...

Ten years ago, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis (FALS) was established. This finding has prompted a myriad of new studies in experimental models aimed at investigating the toxic function of the mutant enzymes. The cellular functions that ...

A common characteristic of familial (fALS) and sporadic amyotrophic lateral sclerosis (sALS) is the accumulation aberrant proteinaceous species in motor neurons spinal cord ALS patients—including aggregates human superoxide dismutase 1 (hSOD1). hSOD1 an enzyme that occurs as a stable dimeric protein with several post-translational modifications such formation intramolecular disulfide bond acqui...

We report the first Italian kindred with Familial Amyotrophic Lateral Sclerosis (FALS) due to c.149T>C mutation in the exon 5 of superoxide dismutase-1 (SOD1) gene. The proband was a 49-year-old woman who came to our observation because of an history of progressive limbs weakness and gait impairment. She belonged to a family of 24 affected members. The prevalent phenotype of the affected member...

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (FALS) by gain of an aberrant function that is not yet well understood. The role of Cu(2+) in mediating the toxicity of mutant SOD1 has been earnestly contested. We tested the in vivo effects of genetically induced copper deprivation on the ALS phenotype of transgenic mice expressing G86R mutant...

Due to novel gene therapy opportunities, genetic screening is no longer restricted familial cases of ALS (FALS) but also aplies the sporadic populations (SALS). Screening four main genes (C9orf72, SOD1, TARDBP and FUS) identified causes in 15% Amyotrophic Lateral Sclerosis (ALS) patients (two third 8% ones) their respective contribution phenotype varies according age disease onset. The overlap ...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a loss of voluntary movement over time, leading to paralysis and death. While 10% of ALS cases are inherited or familial (FALS), the majority of cases (90%) are sporadic (SALS) with unknown etiology. Approximately 20% of FALS cases are genetically linked to a mutation in the anti-oxidizing enzyme, superoxide dis...

Amyotrophic lateral sclerosis (ALS) occurs both sporadically and as a familial disorder (FALS); sporadic and familial forms are clinically indistinguishable and most probably share converging pathogenetic mechanisms. Present evidence indicates that ALS is multifactorial (1), like other late-onset neurodegenerative diseases in which loss of neurones reflects a complex interplay between oxidative...

Mutations in the superoxide dismutase 1 (SOD1) gene have been detected in affected members of some families with familial amyotrophic lateral sclerosis. To evaluate the possibility of a shared genetic defect in amyotrophic lateral sclerosis and Parkinson's disease, the SOD1 gene was sequenced in index patients with familial Parkinson's disease from 23 families. No changes were detected.