There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5-10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the s...

The gene encoding yeast-enhanced green fluorescent protein (GFP) was placed under control of ALS gene promoters in Candida albicans. The PALS-GFP reporter strains were validated using various techniques including a new real-time RT-PCR assay to quantify ALS gene expression. The PALS-GFP reporter strains were grown in media that promoted yeast or germ tube forms, and the resulting fluorescence w...

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease, and the lack of effective therapy results in inevitable death within a few years of onset. Failure of GluA2 RNA editing resulting from downregulation of the RNA-editing enzyme adenosine deaminase acting on RNA 2 (ADAR2) occurs in the majority of ALS cases and causes the death of motor neurons via a Ca(2+) -...

The completion of the Human Genome Project, together with a better understanding of some of the emerging genetic patterns of human disease, has enabled a thorough examination of the most appropriate genetic models for amyotrophic lateral sclerosis (ALS). The pathology and epidemiology of ALS have been intensively studied since Adar, Charcot, and Duchenne first described the disease in the 1860 ...

OBJECTIVE To analyze the ataxin 2 (ATXN2) CAG repeat size in a cohort of patients with amyotrophic lateral sclerosis (ALS) and healthy controls. Large (CAG)(n) alleles of the ATXN2 gene (27-33 repeats) were recently reported to be associated with an increased risk of ALS. DESIGN Case-control study. SETTING France and Quebec, Canada. PARTICIPANTS A total of 556 case patients with ALS and 4...

The ability to precisely engineer plant genomes offers much potential for advancing basic and applied plant biology. Here, we describe methods for the targeted modification of plant genomes using transcription activator-like effector nucleases (TALENs). Methods were optimized using tobacco (Nicotiana tabacum) protoplasts and TALENs targeting the acetolactate synthase (ALS) gene. Optimal TALEN s...

Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and paralysis. No treatment can significantly slow or arrest the disease progression. Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity. In principle, these cases could be treated with RNAi that destroys the mutant mRNA, thereby abolishing the toxic protein. However, no system is available to effi...

The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach ...

Background: It is increasingly clear that common human diseases have a complex genetic architecture characterized, in part, by epistasis or gene-gene interactions. We have previously identified statistically significant gene-gene interactions that replicated across two independent genome-wide association studies (GWAS) of sporadic Amyotrophic Lateral Sclerosis (ALS). The goal of the present stu...

background: despite the genetic heterogeneity reported in familial als (fals), sod1 gene mutations are the most frequent cause of fals, accounting for around 20% of familial cases (als1) and isolated sporadic cases. mutant forms of sod1 exhibit toxicity that promotes the death of motor neurons. it is well documented that fals produces protein aggregates in the motor neurons of fals patients, wh...