Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative condition that results in the death of the large motor neurons of the brain and spinal cord. Familial ALS accounts for 10% of all ALS cases. Approximately 25% of these cases are due to mutations in the SOD1 gene. Several lines of evidence argue that mutant SOD1 causes ALS by a toxic gain of function. We therefore anticipate that measures that reduce the levels of mutant SOD1 expression should be beneficial in mutant SOD1-associated ALS patients. Mitomycin C (MC) is an antitumor antibiotic previously demonstrated to reduce SOD1 expression in a reporter gene system. We investigated whether MC reduces endogenous SOD1 expression levels both in vitro and in vivo. MC reduced human and rat SOD1 protein levels in vitro, with a concomitant decrease in actin and increase in p53 protein levels, as detected by Western blotting. However, this decrease in SOD1 protein levels was paralleled by a similar decrease in cell viability. In contrast, intracerebroventricular administration of MC to rats and mice failed to produce any effect on brain or spinal cord SOD1 protein levels. Our data indicate the apparent inhibition of SOD1 expression by MC is a non-specific consequence of MC-induced cellular toxicity.
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PMID:Inhibition of SOD1 expression by mitomycin C is a non-specific consequence of cellular toxicity. 1624 41

A typical lipidomics approach aims at the simultaneous analysis of a multitude of lipid species from different lipid classes with highest possible sensitivity for all target lipids. Efficient extraction of lipids from the biological matrix is a crucial step in the analytical workflow. Whereas numerous applications of classical and more recently published extraction methods have been reported for blood serum or plasma samples, very little is known about the applicability of these methods for cerebrospinal fluid (CSF). CSF though represents a highly interesting biofluid for the investigation of neurological disorders, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, or brain cancer. Since CSF comprises substantially lower endogenous lipid concentrations compared to serum or plasma, the use of highly efficient extraction methods is of utmost importance. In addition, literature on lipid extraction methods is often inconsistent in terms of methodological parameters like temperature, mixing times, or the number of repeated extraction cycles. In this study, four liquid-liquid extraction methods (Folch, Bligh & Dyer, MTBE and BUME) and one protein precipitation method (MMC method) were evaluated using a pooled CSF sample, followed by the investigation of key process parameters (temperature and mixing times) and modifications of the most promising methods, in order to achieve a broad coverage of lipid classes as well as high recoveries and repeatabilities. A modified Folch method turned out as most suitable for the efficient extraction of a broad range of lipid classes from CSF including glycerophospholipids, glycerolipids and sphingolipids. In addition, using cooled solvents and equipment was shown to significantly improve lipid extraction efficiencies. Mixing times should be thoroughly optimized for the lipid classes of interest in order to achieve high recoveries without lipid degradation due to unnecessarily long mixing. Finally, acidification led to improved extraction efficiency for acidic glycerophospholipids.
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PMID:Evaluation and optimization of common lipid extraction methods in cerebrospinal fluid samples. 3273 23