title: Worming forward: amyotrophic lateral sclerosis toxicity mechanisms and genetic interactions in Caenorhabditis elegans.
abstract: Neurodegenerative diseases share pathogenic mechanisms at the cellular level including protein misfolding, excitotoxicity and altered RNA homeostasis among others. Recent advances have shown that the genetic causes underlying these pathologies overlap, hinting at the existence of a genetic network for neurodegeneration. This is perhaps best illustrated by the recent discoveries of causative mutations for amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Once thought to be distinct entities, it is now recognized that these diseases exist along a genetic spectrum. With this wealth of discoveries comes the need to develop new genetic models of ALS and FTD to investigate not only pathogenic mechanisms linked to causative mutations, but to uncover potential genetic interactions that may point to new therapeutic targets. Given the conservation of many disease genes across evolution, Caenorhabditis elegans is an ideal system to investigate genetic interactions amongst these genes. Here we review the use of C. elegans to model ALS and investigate a putative genetic network for ALS/FTD that may extend to other neurological disorders.
authors.affiliation: Départment de Pathologie et Biologie Cellulaire, CRCHUM-Centre Hospitalier de l'Université de Montréal, Université de Montréal Montréal, QC, Canada.
authors.forename: Martine
authors.initials: M
authors.lastname: Therrien
authors.affiliation: Départment de Pathologie et Biologie Cellulaire, Départment de Neurosciences, CRCHUM-Centre Hospitalier de l'Université de Montréal, Université de Montréal Montréal, QC, Canada.
authors.forename: J Alex
authors.initials: JA
authors.lastname: Parker
keywords: ALS (Amyotrophic lateral sclerosis); C. elegans; C9orf72; FUS; SOD1; TDP-43; genetic networks; motor neuron disease