Ammonium tetrathiomolybdate delays onset, prolongs survival, and slows progression of disease in a mouse model for amyotrophic lateral sclerosis

Dynamic Meta-Analysis as a Therapeutic Prediction Tool for Amyotrophic Lateral Sclerosis

“…Chemistry: encompasses measures of aberrant cellular chemistry, enzymatics, or catalysis (Tiwari, Xu et al 2005;Tokuda, Ono et al 2008) that results in oxidative damage and metal mishandling that can be seen alone or in conjunction with SOD1 mutations. Inflammation: encompasses measures of immune-induced inflammation, including astrocyte (Nagai, Re et al 2007) and microglia (Hall, Andrus et al 1998) counts, gliosis and the release of nitric oxide and proinflammatory cytokines, which in combination with impaired growth factors/trophic support (Narai, Nagano et al 2005;Kadoyama, Funakoshi et al 2007), further inhibit the neural environment.…”

Regulation of Intracellular Copper by Induction of Endogenous Metallothioneins Improves the Disease Course in a Mouse Model of Amyotrophic Lateral Sclerosis

“…lowering strategies in mutant SOD1 mice, including pharmacological chelation [6,11] or the restriction of copper intake [12], support a deleterious role of copper dyshomeostasis in ALS.…”

“…The disease duration was regarded as the period from disease onset until the end point. The motor coordination of mice was measured using a rota-rod apparatus (Muromachi Chemicals, Fukuoka, Japan), as described previously [11].…”

“…Measurement of SOD1 Enzymatic Activity SOD1 enzymatic activity was measured using a SOD1 Assay Kit-WST (Dojindo Molecular Technology Inc., Kumamoto, Japan), as described previously [11]. One unit of SOD1 activity was defined as a 50 % inhibition of the rate of watersoluble tetrazolium salt reduction.…”

Oxidative Stress in Neurodegenerative Diseases

“…Other substances used in preclinical ALS models, i.e., resveratrol, which, when given before disease onset, de cre ase d MDA le ve ls [ 1 06] , a n d am m o n i u m tetrathiomolybdate, which decreased spinal SOD activity [86]. The latter compound also ameliorated ALS-like symptoms in SOD1 G93A mice, probably by chelating the copper ions from the Cys111 site in the SOD-1 enzyme, which is important because various SOD-1 mutations affect Cu and Zn metal-binding, thereby promoting toxic protein aggregation [86].…”