Simple Targeted Assays for Metabolic Pathways and Signaling: A Powerful Tool for Targeted Proteomics.
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ABSTRACT:
SUBMITTER: Kopczynski D
PROVIDER: S-EPMC7586293 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Simple Targeted Assays for Metabolic Pathways and Signaling: A Powerful Tool for Targeted Proteomics.
Kopczynski Dominik D Hentschel Andreas A Coman Cristina C Schebb Nils Helge NH Hornemann Thorsten T Mashek Douglas G DG Hartung Nicole M NM Shevchuk Olga O Schött Hans-Frieder HF Lorenz Kristina K Torta Federico F Burla Bo B Zahedi René P RP Sickmann Albert A Kreutz Michael R MR Ejsing Christer S CS Medenbach Jan J Ahrends Robert R
Analytical chemistry 20200921 20
We introduce STAMPS, a pathway-centric web service for the development of targeted proteomics assays. STAMPS guides the user by providing several intuitive interfaces for a rapid and simplified method design. Applying our curated framework to signaling and metabolic pathways, we reduced the average assay development time by a factor of ∼150 and revealed that the insulin signaling is actively controlled by protein abundance changes in insulin-sensitive and -resistance states. Although at the curr ...[more]
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Project description:We introduce STAMPS, a pathway centric web service for the development of targeted proteomics assays. STAMPS guides the user by providing several intuitive interfaces for a rapid and simplified method design. Applying our curated framework to signaling and metabolic pathways, we reduced average assay development time by a factor of ~150 and revealed that the insulin signaling is actively controlled by protein abundance changes in insulin sensitive and resistance states.
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Project description:OBJECTIVE:Previous gene expression analysis identified a network of coexpressed genes that is associated with β-amyloid neuropathology and cognitive decline in older adults. The current work targeted influential genes in this network with quantitative proteomics to identify potential novel therapeutic targets. METHODS:Data came from 834 community-based older persons who were followed annually, died, and underwent brain autopsy. Uniform structured postmortem evaluations assessed the burden of β-amyloid and other common age-related neuropathologies. Selected reaction monitoring quantified cortical protein abundance of 12 genes prioritized from a molecular network of aging human brain that is implicated in Alzheimer's dementia. Regression and linear mixed models examined the protein associations with β-amyloid load and other neuropathological indices as well as cognitive decline over multiple years preceding death. RESULTS:Average age at death was 88.6 years. Overall, 349 participants (41.9%) had Alzheimer's dementia at death. A higher level of PLXNB1 abundance was associated with more β-amyloid load (p = 1.0 × 10-7 ) and higher PHFtau tangle density (p = 2.3 × 10-7 ), and the association of PLXNB1 with cognitive decline is mediated by these known Alzheimer's disease pathologies. On the other hand, higher IGFBP5, HSPB2, and AK4 and lower ITPK1 levels were associated with faster cognitive decline, and, unlike PLXNB1, these associations were not fully explained by common neuropathological indices, suggesting novel mechanisms leading to cognitive decline. INTERPRETATION:Using targeted proteomics, this work identified cortical proteins involved in Alzheimer's dementia and begins to dissect two different molecular pathways: one affecting β-amyloid deposition and another affecting resilience without a known pathological footprint. Ann Neurol 2018;83:78-88.
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