氧化还原蛋白质组学鉴定遗传性阿尔茨海默病中氧化修饰的脑蛋白：初步评估

Redox proteomics identification of oxidatively modified brain proteins in inherited Alzheimer's disease: an initial assessment.

作者信息

Butterfield D Allan, Gnjec Anastazija, Poon H Fai, Castegna Alessandra, Pierce William M, Klein Jon B, Martins Ralph N

机构信息

Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA.

出版信息

J Alzheimers Dis. 2006 Dec;10(4):391-7. doi: 10.3233/jad-2006-10407.

DOI:10.3233/jad-2006-10407

PMID:17183150

Abstract

OBJECTIVE

To identify oxidatively modified proteins in brains of persons with inherited Alzheimer's disease.

METHODS

Redox proteomics was used to identify oxidatively modified brain proteins in persons with mutations in the genes for presenilin-1 (PS-1).

RESULTS

An initial redox proteomics assessment of oxidatively modified proteins from brains of individuals with PS-1 mutations was performed. These PS1 mutations, Q222H and M233T, are completely penetrant causing early-onset familial AD as previously reported in these Australian families. We show that oxidative modifications of ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), gamma-enolase, actin, and dimethylarginine dimethylaminohydrolase 1 (DMDMAH-1) are present in the brain of familial AD subjects.

CONCLUSIONS

These initial results suggest that oxidatively modified proteins are important common features in both familial and sporadic AD.

摘要

目的

鉴定遗传性阿尔茨海默病患者大脑中氧化修饰的蛋白质。

方法

采用氧化还原蛋白质组学方法鉴定早老素-1（PS-1）基因突变患者大脑中氧化修饰的脑蛋白。

结果

对携带PS-1基因突变个体大脑中氧化修饰蛋白质进行了初步的氧化还原蛋白质组学评估。这些PS1突变，即Q222H和M233T，具有完全的外显率，可导致早发性家族性阿尔茨海默病，如先前在这些澳大利亚家族中所报道的。我们发现，泛素羧基末端水解酶L1（UCH-L1）、γ-烯醇化酶、肌动蛋白和二甲基精氨酸二甲基氨基水解酶1（DMDMAH-1）的氧化修饰存在于家族性阿尔茨海默病患者的大脑中。