title: ALS genetic modifiers that increase survival of SOD1 mice and are suitable for therapeutic development.
abstract: Amyotrophic lateral sclerosis (ALS) is a frequently fatal motor neuron disease without any cure. To find molecular therapeutic targets, several studies crossed transgenic ALS murine models with animals transgenic for some ALS target genes. We aimed to revise the new discoveries and new works in this field. We selected the 10 most promising genes, according to their capability when down-regulated or up-regulated in ALS animal models, for increasing life span and mitigating disease progression: XBP-1, NogoA and NogoB, dynein, heavy and medium neurofilament, NOX1 and NOX2, MLC-mIGF-1, NSE-VEGF, and MMP-9. Interestingly, some crucial modifier genes have been described as being involved in common pathways, the most significant of which are inflammation and cytoskeletal activities. The endoplasmic reticulum also seems to play an important role in ALS pathogenesis, as it is involved in different selected gene pathways. In addition, these genes have evident links to each other, introducing the hypothesis of a single unknown, common pathway involving all of these identified genes and others to be discovered.
authors.affiliation: Department of Neurological Sciences, Dino Ferrari Centre, University of Milan, IRCCS Fondazione Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Riboldi
authors.forename: Monica
authors.initials: M
authors.lastname: Nizzardo
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.forename: Marianna
authors.initials: M
authors.lastname: Falcone
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1