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

Power3 Medical Products, Inc., The Woodlands, TX, USA.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 05/2006; 342(4):1034-9. DOI: 10.1016/j.bbrc.2006.02.051
Source: PubMed


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, Bb, and Pre-Serum amyloid protein displayed different serum concentrations in ALS, PD, and normal sera, whereas Complement C4b gamma-chain and Complement Factor I 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 of ALS and PD.

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Available from: Albert A Yen, Dec 12, 2013
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    • "The complement system is part of the non-specific immune system. Using 2D-gel-electrophoresis, Goldknopf et al. (2006) found differences in serum levels of nine complement factors between PD and controls. Osteopontin is a molecule with multiple functions, including modulation of inflammatory response of microglia, and shows much higher levels in CSF than in serum. "
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    ABSTRACT: Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson's disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.
    Journal of Neural Transmission 07/2011; 119(1):39-52. DOI:10.1007/s00702-011-0682-x · 2.40 Impact Factor
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    • "There are also abnormalities of complement in ALS. Two dimensional gel electrophoresis was used to study serum proteins in ALS subjects and found that components of complement C3 were increased compared to controls [95]. There is also evidence of low level systemic inflammation with increased levels of C reactive protein and ESR in subjects with ALS compared to controls, with the levels correlating the levels of disability as measured by the ALS functional rating scale [96]. "
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    ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a severe progressive neurodegenerative disease. The cause is unknown, but genetic abnormalities have been identified in subjects with familial ALS and also in subjects with sporadic ALS. Environmental factors such as occupational exposure have been shown to be risk factors for the development of ALS. Patients differ in their clinical features and differ in the clinical course of disease. Immune abnormalities have been found in the central nervous system by pathological studies and also in the blood and CSF of subjects with ALS. Inflammation and immune abnormalities are also found in animals with a model of ALS due to mutations in the SOD1 gene. Previously it has been considered that immune abnormalities might contribute to the pathogenesis of disease. However more recently it has become apparent that an immune response can occur as a response to damage to the nervous system and this can be protective.
    Current Molecular Medicine 03/2011; 11(3):246-54. DOI:10.2174/1566211213754895240 · 3.62 Impact Factor
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    • "Indeed, differences have been reported between the components of complement C3c and complement factor H and B in affected subjects compared to controls. Differential expression of complement proteins may represent potentially useful BMs for ALS and PD [169]. These findings lend further support to evidence suggesting that inflammatory processes involving complement cascade elements may be involved in the onset of PD. "
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    ABSTRACT: Neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD) are considered disorders of multifactorial origin, inevitably progressive and having a long preclinical period. Therefore, the availability of biological markers or biomarkers (BMs) for early disease diagnosis will impact the management of AD and PD in several dimensions; it will 1) help to capture high-risk individuals before symptoms develop, a stage where prevention efforts might be expected to have their greatest impact; 2) provide a measure of disease progression that can be evaluated objectively, while clinical measures are much less accurate; 3) help to discriminate between true AD or PD and other causes of a similar clinical syndrome; 4) delineate pathophysiological processes responsible for the disease; 5) determine the clinical efficacy of novel, disease-modifying (neuroprotective) strategies. In the long run the availability of reliable BMs will significantly advance the research and therapeutics of AD and PD.
    06/2010; 1(2). DOI:10.1007/s13167-010-0036-z
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