Biomarker discovery in neurodegenerative diseases: A proteomic approach

Department of Pathology, University of Washington School of Medicine, HMC Box 359635, 325 9th Avenue, Seattle, WA 98104, USA.
Neurobiology of Disease (Impact Factor: 5.08). 10/2008; 35(2):157-64. DOI: 10.1016/j.nbd.2008.09.004
Source: PubMed


Biomarkers for neurodegenerative disorders are essential to facilitate disease diagnosis, ideally at early stages, monitor disease progression, and assess response to existing and future treatments. Application of proteomics to the human brain, cerebrospinal fluid and plasma has greatly hastened the unbiased and high-throughput searches for novel biomarkers. There are many steps critical to biomarker discovery, whether for neurodegenerative or other diseases, including sample preparation, protein/peptide separation and identification, as well as independent confirmation and validation. In this review we have summarized current proteomics technologies involved in discovery of biomarkers for neurodegenerative diseases, practical considerations and limitations of several major aspects, as well as the current status of candidate biomarkers revealed by proteomics for Alzheimer and Parkinson diseases.

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Available from: Min Shi, Oct 02, 2015
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    • "However , as pointed by Shi and colleagues, the biomarker might be present in the CFS only at later stages of NDs, no longer being useful for early diagnosis or intervention. Hence it is desirable that a biomarker would first be detectable in the blood and subsequently in the CSF, if possible [22]. Proteomic approaches applied in studies of the CNS performed with embryonic and postnatal brain tissue, different brain regions, CSF, neural stem cells, pre and post synaptic proteomes and neurodegenerative diseases were extensively reviewed by Zang [23]. "
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    ABSTRACT: Alzheimer´s and Parkinson´s diseases are severe neurodegenerative conditions triggered by complex biochemical routes. Many groups are currently pursuing the search for valuable biomarkers to either perform early diagnostic or to follow the disease's progress. Several studies have reported relevant findings regarding environmental issues and the progression of such diseases. Here the etiology and mechanisms of these diseases are briefly reviewed. Approaches that might reveal candidate biomarkers and environmental stressors associated to the diseases were analyzed under a proteomic perspective. This article is part of a Special Issue entitled: Environmental and structural proteomics.
    Journal of proteomics 04/2014; 104. DOI:10.1016/j.jprot.2014.04.014 · 3.89 Impact Factor
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    • "In addition, neurodegeneration is clinically heterogeneous, with multiple subtypes associated with different survival times, rates of progression and symptoms. Robust biomarkers would be valuable not only for the initial diagnosis, but the classification of various subtypes of disease, monitoring responses to therapeutic agents and tracking disease progression (Shi et al., 2009). "
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    ABSTRACT: MicroRNAs (miRNAs) are small, abundant RNA molecules that constitute part of the cell's non-coding RNA "dark matter." In recent years, the discovery of miRNAs has revolutionised the traditional view of gene expression and our understanding of miRNA biogenesis and function has expanded. Altered expression of miRNAs is increasingly recognized as a feature of many disease states, including neurodegeneration. Here, we review the emerging role for miRNA dysfunction in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease pathogenesis. We emphasize the complex nature of gene regulatory networks and the need for systematic studies, with larger sample cohorts than have so far been reported, to reveal the most important miRNA regulators in disease. Finally, miRNA diversity and their potential to target multiple pathways, offers novel clinical applications for miRNAs as biomarkers and therapeutic agents in neurodegenerative diseases.
    Frontiers in Cellular Neuroscience 10/2013; 7:178. DOI:10.3389/fncel.2013.00178 · 4.29 Impact Factor
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    • "Examination of various tissues and body fluids for the relative levels of proteins and other molecules provides information about the state of the local system, including its metabolic state, disease condition, and response to therapeutic treatments. Therefore, measurement of a number of known small proteins and other molecules along with unbiased profiling (recently reviewed elsewhere [53,54]) is currently one of the most promising avenues for potential premotor biomarkers of PD (Table 1). "
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    ABSTRACT: The second most serious neurodegenerative disease is Parkinson's disease (PD). Over the past several decades, a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear. Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders, screen novel therapeutics, and predict eventual clinical PD before the onset of symptoms. Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area. Moreover, other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid, blood, or saliva. Finally, interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers. The current review highlights recent advances and underscores areas of potential advancement.
    Translational Neurodegeneration 05/2012; 1(1):11. DOI:10.1186/2047-9158-1-11
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