1,721,066 research outputs found
Lessons from models of SOD1-linked familial ALS
No full textTen years ago, the linkage between mutations in the gene coding for the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) and the neurodegenerative disease known as familial amyotrophic lateral sclerosis (FALS) was established. This finding has prompted a myriad of new studies in experimental models aimed at investigating the toxic function of the mutant enzymes. The cellular functions that are impaired in motoneurons as a consequence of molecular alterations induced by the expression of FALS SOD1 converge on pathways that might be activated in sporadic ALS by other toxic factors. Recent data demonstrate that, although motoneurons are lost in patients, other cell types are also affected and actively contribute to the pathogenesis of the disease
Targets in ALS: designing multidrug therapies
No full textAmyotrophic lateral sclerosis (ALS) is an incurable disease that arises from the progressive loss of motoneurons. Even when caused by a single gene defect, as in the case of mutations in the enzyme Cu-Zn superoxide dismutase (SOD1), ALS is the result of a complex cascade that involves crosstalk among motoneurons, glia and muscles, and evolves through the action of converging toxic mechanisms. Transgenic rodents that express human mutant SOD1 and develop a progressive paralytic disease are widely used to screen potential therapeutics. Treatments that interfere with a specific event in the neurotoxic cascade have been reported to produce a modest increase in rodent lifespan. Multi-intervention approaches, including novel methods to intercept the damage and to deliver molecules to vulnerable cells, have recently been shown to be more effective. Thus, new avenues for promising therapeutic approaches can be derived from multidrug treatments and/or the delivery of growth factors by viral vectors, in combination with exercise and/or diet regimens
Studio dell'effetto del trattamento con FANS sul metabolismo mitocondriale del muscolo scheletrico in un modello murino di sclerosi laterale amiotrofica familiare
No full textIn situ hybridization histochemistry quantification: automatic count on single cell in digital image
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Automatic quantitative evaluation of autoradiographic band films by computerized image analysis
No full textTreatment with lithium carbonate does not improve disease progression in two different strains of SOD1 mutant mice
No full textIt has been shown that chronic treatment with lithium carbonate (Li(2)CO(3)) in presymptomatic SOD1G93A transgenic male mice, a model of ALS, was able to remarkably increase their lifespan through the activation of autophagy and the promotion of mitochondriogenesis and neurogenesis. This prompted us to test the lithium effect also in female SOD1G93A mice with two phenotypes of different disease severity. Female SOD1G93A mice of C57BL/6J or 129S2/Sv genetic background were treated daily with Li(2)CO(3) 37 mg/kg (1 mEq/kg) i.p. starting from age 75 days until death. Grip strength, latency to fall on rotarod and body weight were monitored twice weekly. At the time of death the spinal cord was removed to assess the number of motor neurons and to measure the expression of a marker of autophagy (LCII) and the activity of mitochondrial complex IV. We observed a significant anticipation of the onset and reduced survival in 129Sv/G93A and no effect in C57/G93A mice treated with lithium compared to vehicle treated mice. Moreover, lithium neither exerted neuroprotective effects nor increased the expression of LCII and the activity of mitochondrial complex IV in the spinal cord. The present study does not identify any therapeutic or neuroprotective effect of lithium in SOD1G93A female mice
The rate of Wallerian degeneration is not affected by reduced expression of endogenous NMNAT1
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