The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.

Electromagnetic radiation (EMR) is emitted from electromagnetic fields that surround power lines, household appliances and mobile phones. Research has shown that there are connections between EMR exposure and cancer and also that exposure to EMR may result in structural damage to neurons. In a study by Salford et al. (Environ Health Perspect 111:881-883, 2003) the authors demonstrated the presence of strongly stained areas in the brains of rats that were exposed to mobile phone EMR. These darker neurons were particularly prevalent in the hippocampal area of the brain. The aim of our study was to further investigate the effects of EMR. Since the hippocampus is involved in learning and memory and emotional states, we hypothesised that EMR will have a negative impact on the subject's mood and ability to learn. We subsequently performed behavioural, histological and biochemical tests on exposed and unexposed male and female rats to determine the effects of EMR on learning and memory, emotional states and corticosterone levels. We found no significant differences in the spatial memory test, and morphological assessment of the brain also yielded non-significant differences between the groups. However, in some exposed animals there were decreased locomotor activity, increased grooming and a tendency of increased basal corticosterone levels. These findings suggested that EMR exposure may lead to abnormal brain functioning.

ObjectiveAs structural variations may underpin susceptibility to complex neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), the objective of this study was to investigate a structural variant (SV) within sequestosome 1 (SQSTM1). MethodsA candidate insertion/deletion variant within intron 5 of the SQSTM1 gene was identified using a previously established SV evaluation algorithm and chosen according to its subsequent theoretical effect on gene expression. The variant was systematically assessed through PCR, polyacrylamide gel fractionation, Sanger sequencing, and reverse transcriptase PCR. ResultsA reliable and robust assay confirmed the polymorphic nature of this variant and that the variant may influence SQSTM1 transcript levels. In a North American cohort of patients with familial ALS (fALS) and sporadic ALS (sALS) (n = 403) and age-matched healthy controls (n = 562), we subsequently showed that the SQSTM1 variant is associated with fALS (p = 0.0036), particularly in familial superoxide dismutase 1 mutation positive patients (p = 0.0005), but not with patients with sALS (p = 0.97). ConclusionsThis disease association highlights the importance and implications of further investigation into SVs that may provide new targets for cohort stratification and therapeutic development. sclerosis gene with amyotrophic lateral SQSTM1 Association of a structural variant within theThis information is current as of February 27, 2020 Services Updated Information & http://ng.neurology.org/content/6/2/e406.full.html including high resolution figures, can be found at: References http://ng.neurology.org/content/6/2/e406.full.html##ref-list-1 This article cites 38 articles, 4 of which you can access for free at: Subspecialty Collections http://ng.neurology.org//cgi/collection/association_studies_in_genetics Association studies in genetics http://ng.neurology.org//cgi/collection/amyotrophic_lateral_sclerosis_ Amyotrophic lateral sclerosis http://ng.neurology.org//cgi/collection/all_neuromuscular_disease All Neuromuscular Disease http://ng.neurology.org//cgi/collection/all_genetics All Genetics following collection(s): This article, along with others on similar topics, appears in the Permissions & Licensing http://ng.neurology.org/misc/about.xhtml#permissions its entirety can be found online at: Information about reproducing this article in parts (figures,tables) or in Reprints http://ng.neurology.org/misc/addir.xhtml#reprintsus Information about ordering reprints can be found online: reserved. Online