title: New Insights on the Mechanisms of Disease Course Variability in ALS from Mutant SOD1 Mouse Models.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disease in terms of progression rate and survival. This is probably one of the reasons for the failure of many clinical trials and the lack of effective therapies. Similar variability is also seen in SOD1(G93A) mouse models based on their genetic background. For example, when the SOD1(G93A) transgene is expressed in C57BL6 background the phenotype is mild with slower disease progression than in the 129Sv mice expressing the same amount of transgene but showing faster progression and shorter lifespan. This review summarizes and discusses data obtained from the analysis of these two mouse models under different aspects such as the motor phenotype, neuropathological alterations in the central nervous system (CNS) and peripheral nervous system (PNS) and the motor neuron autonomous and non-cell autonomous mechanisms with the aim of finding elements to explain the different rates of disease progression. We also discuss the identification of promising prognostic biomarkers by comparative analysis of the two ALS mouse models. This analysis might possibly suggest new strategies for effective therapeutic intervention in ALS to slow significantly or even block the course of the disease.
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nardo
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Trolese
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tortarolo
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vallarola
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.|Animal Facility, AriSLA, Fondazione Italiana di ricerca per la Sclerosi Laterale Amiotrofica.
authors.forename: Mattia
authors.initials: M
authors.lastname: Freschi
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Laboratory of Translational Proteomics, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pasetto
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Laboratory of Translational Proteomics, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bonetto
authors.affiliation: Department of Neuroscience, Laboratory Molecular Neurobiology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1
keywords: Transgenic SOD1G93A mice; biomarkers; disease course variability; motor neuron; peripheral motor system