There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disease, is caused by gene--environment interactions. In fact, given that only about 10% of all ALS diagnosis has a genetic basis, gene-environmental interaction may give account for the remaining percentage of cases. However, relatively little attention has been paid to environmental and lifes...

A reason for screening amyotrophic lateral sclerosis (ALS) patients for mutations in the superoxide dismutase-1 (SOD1) gene is the opportunity to find novel mutations with properties that can give information on pathogenesis. A novel c.352C>G (L117V) SOD1 mutation was found in two Syrian ALS families living in Europe. The disease showed unusually low penetrance and slow progression. In erythroc...

The FUS gene has been linked to amyotrophic lateral sclerosis (ALS). FUS is a ubiquitous RNA-binding protein, and the mechanisms leading to selective motoneuron loss downstream of ALS-linked mutations are largely unknown. We report the transcriptome analysis of human purified motoneurons, obtained from FUS wild-type or mutant isogenic induced pluripotent stem cells (iPSCs). Gene ontology analys...

Amyotrophic lateral sclerosis (ALS) is a lethal degenerative disorder of motoneurons, which may occur concurrently with frontotemporal dementia. Genetic analyses of the 10% of ALS cases that are dominantly inherited provide insight into ALS pathobiology. Two broad themes are evident. One, prompted by investigations of the SOD1 gene, is that conformational instability of proteins triggers downst...

29 Introduction Amyotrophic Lateral Sclerosis (ALS), commonly known as “Lou Gehrig’s Disease,” is a fatal neurodegenerative disorder characterized by the slow degeneration of the motor neurons (MNs) of the entire human body, including, but not limited to, the MNs of the cerebral cortex, spinal cord and limb, axial and respiratory muscles. ALS is an adult-onset, rapidly progressive disease, kill...

IntroductIon Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of upper motor neurons (UMNs) and lower motor neurons (LMNs), typically may die from respiratory failure within 2–5 years of symptom onset.[1] About 10% of ALS patients are familial whereas the remaining patients are sporadic. ALS is highly heterogeneous in genetic and cl...

The "mini-epidemic" distribution of rare conditions (either sporadic, inherited or due to a transmissible agent) is frequently described as a cluster. Genetic abnormalities and environmental factors are usually investigated to explain the presence of a disease cluster. We have reported a cluster of amyotrophic lateral sclerosis (ALS) cases in a small area of central Italy, where an identical SO...

Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are severe nervous system diseases characterized by the degeneration of lower motor neurons. They share a number of additional pathological, cellular, and genetic parallels suggesting that mechanistic and clinical insights into one disorder may have value for the other. While there are currently no clinical ALS gene therapies...

Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by motor neuron degeneration. A subgroup of familial cases arises from mutations in the gene encoding cytosolic superoxide dismutase (SOD1). This review considers insight now being gained into ALS pathogenesis from the study of mutant SOD1 protein and its possible mechanisms of adverse effect on nerve cells. Also dis...