首页 | 本学科首页   官方微博 | 高级检索  
     


Misfolded superoxide dismutase-1 in CSF from amyotrophic lateral sclerosis patients
Authors:Zetterström Per  Andersen Peter M  Brännström Thomas  Marklund Stefan L
Affiliation:1. Department of Medical Biosciences, Clinical Chemistry, Ume? University, Ume?, Sweden;2. Department of Pharmacology and Clinical Neuroscience, Ume? University, Ume?, Sweden;3. Department of Medical Biosciences, Pathology, Ume? University, Ume?, Sweden
Abstract:Several of the superoxide dismutase-1 (SOD1) mutations linked to amyotrophic lateral sclerosis (ALS) lead to synthesis of structurally defective molecules, suggesting that any cytotoxic conformational species common for all mutations should be misfolded. SOD1 can be secreted and evidence from ALS model systems suggests that extracellular SOD1 may be involved in cytotoxicity. Three ELISAs specifically reacting with different sequence segments in misfolded SOD1 species were used for analysis of CSF from 38 neurological controls and from 96 ALS patients, 57 of whom were sporadic cases and 39 familial, including 22 patients carrying SOD1 mutations. Misfolded SOD1 was found in all samples. There were, however, no significant differences between patients with and without mutations, and between all the ALS patients and the controls. The estimated concentration of misfolded SOD1 in the interstitium of the CNS is a 1000 times lower than that required for appreciable cytotoxicity in model systems. The results argue against a direct cytotoxic role of extracellular misfolded SOD1 in ALS. Misfolded SOD1 in CSF cannot be used as a biomarker of ALS in patients with and without mutations in the enzyme.
Keywords:amyotrophic lateral sclerosis  biomarker  CSF  ELISA  misfolding  superoxide dismutase‐1
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号