The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech-nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients ( = 60) compared to controls ( = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that bound with high specificity to each target group. Based on this, we synthesized two unique X-aptamer sequences, and specific proteins pulled down from the patient and control groups by these X-aptamers were identified by mass spectrometry. We identified two protein biomarkers, complement component C4A and ApoB, upregulated in plasma samples from schizophrenia patients. ELISA validation suggested that the observed differences in C4 levels in patients are likely due to the presence of the illness itself, while ApoB may be a marker of antipsychotic-induced alterations. These studies highlight the utility of the X-aptamer technology in the identification of biomarkers for schizophrenia that will advance our understanding of the pathophysiological mechanisms of this disorder.
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http://dx.doi.org/10.1159/000492331 | DOI Listing |
Genes Dis
September 2023
Department of Neurosurgery and Neuroscience Institute, Baylor Scott & White Health, Temple, TX 76508, USA.
Mol Neuropsychiatry
March 2019
Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
The field of proteomics is rapidly gaining territory as a promising alternative to genomic approaches in the efforts to unravel the complex molecular mechanisms underlying schizophrenia and other psychiatric disorders. X-aptamer tech-nology has emerged as a novel proteomic approach for high-sensitivity analyses, and we hypothesized that this technology would identify unique molecular signatures in plasma samples from schizophrenia patients ( = 60) compared to controls ( = 20). Using a combinatorial library of X-aptamer beads, we developed a two-color flow cytometer-based approach to identify specific X-aptamers that bound with high specificity to each target group.
View Article and Find Full Text PDFMethods Mol Biol
April 2018
Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center, 1825 Pressler Street, Houston, TX, 77030, USA.
Aptamers and second generation analogs, such as X-Aptamers (XAs), SOMAmers, locked nucleic acids (LNAs), and others are increasingly being used for molecular pathway targeting, biomarker discovery, or disease diagnosis by interacting with protein targets on the surface of cells or in solution. Such targeting is being used for imaging, diagnostic evaluation, interference of protein function, or delivery of therapeutic agents. Selection of aptamers using the original SELEX method is cumbersome and time-consuming, often requiring 10-15 rounds of selection, and provides aptamers with a limited number of functional groups, namely four bases of DNA or RNA, although newer SELEX methods have increased this diversity.
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