RNA sequencing to identify common targets for regulation of cognition
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE83217 | GEO | 2017/06/10
SECONDARY ACCESSION(S): PRJNA325293
REPOSITORIES: GEO
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Project description:Cognitive decline in aging is a major issue, causing both personal and economic hardship in an increasingly aging society. There are several known individual misfolded proteins that cause issues with age, such as amyloid beta and alpha synuclein. However, many studies have found that the proteostasis network, which works to keep proteins properly folded, is impaired with age, suggesting that there may be more global protein structural changes. We used limited-proteolysis mass spectrometry (LiP-MS) to investigate protein structural changes proteome-wide in a rodent model of aging. We compared hippocampi from aged rodents with normal cognition (aged unimpaired, AU) to hippocampi from aged rodents with impaired cognition (aged impaired, AI). We identified several hundred proteins as Cognition-Associated Structural Changes (CASCs), which are structurally different between the AU and AI populations. We found correlations between these trends and those of protein refoldability, a separate measure of how well a protein can independently refold to its native state after complete denaturation. CASCs were enriched with nonrefoldable proteins. Potential confounding factors of our study such as LiP reproducibility and post-translational modifications were assessed. Searches for oxidation and phosphorylation did not yield significant differences between AU and AI samples within each hippocampal region. Our study overall suggests that neuronal protein structural changes are global in nature and are more often intrinsically nonrefoldable, which may partially explain their susceptibility to structural changes due to proteostasis network breakdown in age.
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