MassIVE MSV000086234

Partial Public

A Temporal Quantitative Profiling of Newly Synthesized Proteins during Abeta Accumulation

Description

Accumulation of aggregated amyloid beta in the brain is believed to impair multiple cellular pathways and play a central role in Alzheimer disease pathology. But how this process is regulated remains unclear. In theory, measuring protein synthesis is the most direct way to evaluate a cell response to stimuli, but to date there have been few reliable methods to do this. To identify the protein regulatory network during the development of Abeta deposition in AD, we applied a new proteomic technique to quantitate newly synthesized protein (NSP) changes in the cerebral cortex and hippocampus of 2-, 5- and 9-month-old APP/PS1 AD transgenic mice. This bioorthogonal non-canonical amino acid tagging analysis combined PALM (Pulse Azidohomoalanine Labeling in Mammals) and HILAQ (Heavy Isotope Labeled AHA Quantitation) to reveal a comprehensive dataset of NSPs prior to and post Abeta deposition, including the identification of proteins not previously associated with AD, and demonstrated that the pattern of differentially expressed NSPs is age dependent. We also found dysregulated vesicle transportation networks including endosomal subunits, coat protein complex I (COPI) and mitochondrial respiratory chain throughout all time points and two brain regions. These results point to a pathological dysregulation of vesicle transportation that occurs prior to Abeta accumulation and the onset of AD symptoms, which may progressively impact the entire protein network and thereby drive neurodegeneration. This study illustrates key pathway regulation responses to the development of AD pathogenesis by directly measuring the changes in protein synthesis and provides unique insights into the mechanisms that underlie AD. [doi:10.25345/C55F5F] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Quantitative profiling ; Newly synthesized proteins ; Abeta accumulation ; alzheimer

Contact

Principal Investigators:
(in alphabetical order)
John R.Yates III, The Scripps Research Institute, united states
Submitting User: yuanhui
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Identification Results
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Quantification Results
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
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