Complement C3c and related protein biomarkers in amyotrophic lateral sclerosis and Parkinson's disease

被引：104
作者：
Goldknopf, IL [1 ]
Sheta, EA
Bryson, J
Folsom, B
Wilson, C
Duty, J
Yen, AA
Appel, SH
机构：
[1] Power3 Med Prod Inc, The Woodlands, TX 77387 USA
[2] Methodist Neurol Inst, Houston, TX USA
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2006年 / 342卷 / 04期
关键词：
amytrophic lateral sclerosis; Parkinson's; neurodegenerative; proteomic; LC-MS/MS; two-dimensional electrophoresis; immune; inflammation; complement; phosphorylation;
D O I：
10.1016/j.bbrc.2006.02.051
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We have used quantitative 2D gel electrophoresis to analyze serum proteins from 422 patients with neurodegenerative diseases and normal individuals in an unbiased approach to identify biomarkers. Differences in abnormal serum levels were found between amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and related disorders for 34 protein biomarker spots, nine of which were related to the complement system. Of these nine, four spots originated from the Complement C3b-alpha-chain (C3c(1), C3c(2a), C3c(2b), and C3dg). The C3c spots (C3c(1), C3c(2a), and C3c(2b)) had the same amino acid sequence and glycosylation, though only C3c(1) was phosphorylated. In addition, Complement Factors H, Hb, and Pre-Serum amyloid protein displayed different serum concentrations in ALS, PD, and normal sera, whereas Complement C4b gamma-chain and Complement Factor 1 did not. The differential expression of the complement proteins provides potentially useful biomarkers as well as evidence for the involvement of inflammatory processes in the pathogenesis or ALS and PD. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码：1034 / 1039
页数：6
相关论文
共 52 条
[1]   Mass spectrometry-based proteomics [J].
Aebersold, R ;
Mann, M .
NATURE, 2003, 422 (6928) :198-207
[2]   Immune reactivity in a mouse model of familial ALS correlates with disease progression [J].
Alexianu, ME ;
Kozovska, M ;
Appel, SH .
NEUROLOGY, 2001, 57 (07) :1282-1289
[3]   HIGH-RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS OF HUMAN-PLASMA PROTEINS [J].
ANDERSON, L ;
ANDERSON, NG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1977, 74 (12) :5421-5425
[4]   The human plasma proteome - History, character, and diagnostic prospects [J].
Anderson, NL ;
Anderson, NG .
MOLECULAR & CELLULAR PROTEOMICS, 2002, 1 (11) :845-867
[5]  
ANNUNZIATA P, 1985, ACTA NEUROL SCAND, V72, P61
[6]   Monoglucosylated glycans in the secreted human complement component C3: implications for protein blosynthesis and structure [J].
Crispin, MDM ;
Ritchie, GE ;
Critchley, AJ ;
Morgan, BP ;
Wilson, IA ;
Dwek, RA ;
Sim, RB ;
Rudd, PM .
FEBS LETTERS, 2004, 566 (1-3) :270-274
[7]   Molecular pathways of neurodegeneration in Parkinson's disease [J].
Dawson, TM ;
Dawson, VL .
SCIENCE, 2003, 302 (5646) :819-822
[8]   SERUM AMYLOID-P COMPONENT BINDING TO C4B-BINDING PROTEIN [J].
DE FRUTOS, PG ;
HARDIG, Y ;
DAHLBACK, B .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (45) :26950-26955
[9]  
EKDAHL KN, 1995, J IMMUNOL, V154, P6502
[10]   Phosphorylation of complement component C3 after synthesis in U937 cells by a putative protein kinase, casein kinase 2, which is regulated by CD11b: evidence that membrane-bound proteases preferentially cleave phosphorylated C3 [J].
Ekdahl, KN ;
Nilsson, B .
BIOCHEMICAL JOURNAL, 1997, 328 :625-633
123456