title: Specific electron transport chain abnormalities in amyotrophic lateral sclerosis.
abstract: In an amyotrophic lateral sclerosis (ALS) patient who also had an IgA gammopathy, autopsy studies identified the IgA in the surviving motor neurons. Further, the IgA bound the surface of isolated bovine motor neurons and inhibited neuronal proliferation in culture. To determine the pathologic basis of this IgA interaction with motor neurons, a neuroblastoma cDNA library was generated and screened with the IgA monoclonal antibody. Reactive clones were identified as flavin adenine dinucleotide (FAD) synthetase. To extend this finding to ALS in general, quantitative RT-PCRs were performed on blood samples from 26 ALS and 30 control blood samples to determine mRNA expression levels of FAD synthetase and other electron transport chain proteins, specifically riboflavin kinase (RFK), cytochrome C1 (CYC1), and succinate dehydrogenase complex subunit B (SDHB). All expression levels were measured against a control enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Expression levels for a non-respiratory chain protein (beta-actin) were also measured. We found that FAD synthetase expression levels were decreased in ALS samples compared to expression levels in controls (P = 0.0151). Expression levels for RFK, CYC1, and SDHB were also significantly decreased in the ALS group (P = 0.0025, P = 0.0002, and P < 0.0001, respectively). As control, expression levels for beta-actin did not show a significant difference between ALS and control groups (P = 0.2118). Our data show that a reduction in electron transport proteins, namely FAD synthetase, RFK, CYC1, and SDHB, is seen in patients with ALS. It is possible that this may have an effect on oxygen-dependent metabolic pathways. Human motor neurons may be particularly susceptible to injury if there is sub-optimal oxidative metabolism.
authors.affiliation: Multiple Sclerosis Research Center of New York, 521 West 57th Street, 4th Fl., New York, NY 10019, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Diamanduros
authors.forename: Soheli A
authors.initials: SA
authors.lastname: Chowdhury
authors.forename: Stephen
authors.initials: S
authors.lastname: Scelsa
authors.forename: Norman
authors.initials: N
authors.lastname: Latov
authors.forename: Saud A
authors.initials: SA
authors.lastname: Sadiq
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000276:immunology; D002478:Cells, Cultured; D003575:Cytochromes c1 / Q000172:deficiency; D015536:Down-Regulation / Q000276:immunology; D004734:Energy Metabolism / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D009046:Motor Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009713:Nucleotidyltransferases / Q000172:deficiency* / Q000276:immunology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency; D013385:Succinate Dehydrogenase / Q000172:deficiency
chemical_list: D007070:Immunoglobulin A; D003575:Cytochromes c1; C108095:SDHB protein, human; D013385:Succinate Dehydrogenase; D017853:Phosphotransferases (Alcohol Group Acceptor); C022532:riboflavin kinase; D009713:Nucleotidyltransferases; C020143:FMN adenylyltransferase