PXD053288

PXD053288 is an original dataset announced via ProteomeXchange.

Title	RyR2-mediated calcium leak increases glyoxalase I in the aging brain
Description	Ryanodine receptor 2 (RyR2) mediated chronic calcium leak in the brain has been implicated in patients with late-onset Alzheimer’s disease (LOAD) and from aging macaques, but the direct downstream consequences of calcium leak remain unclear. Here, we present that RyR2 mediated chronic calcium leak leads to increased glyoxalase 1 (GLO1), a major scavenger of pro-oxidant, inflammatory dicarbonyl compounds, expression and activity. Our aging macaque model revealed significantly increased GLO1 expression in the prefrontal cortex (PFC) and entorhinal cortex with age, which correlated with increased calcium leak through RyR2. We characterized GLO1 cellular and ultrastructural localization in dendrites, axon terminals, and astrocytes in the aged macaque dorsolateral PFC. To test causation, we used a knockin mouse model which replaces the serine at 2808 with aspartic acid (S2808D-RyR2), causing calcium leak through RyR2. We report significantly increased GLO1 expression and activity in S2808D-RyR2 PFC and hippocampus, as early as 1-month-old and as late as 21-month-old. This increase was driven by several cell types. The publicly available proteomics data set generated from synaptosomes from S2808D-RyR2 illuminate the downstream effects of elevated calcium in vulnerable areas of the brain. These results further elucidate the role of GLO1 in neurodegeneration and the aging brain.
HostingRepository	PRIDE
AnnounceDate	2025-09-25
AnnouncementXML	Submission_2025-09-25_07:19:06.706.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	methylthiolated residue; monohydroxylated residue; deaminated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-21 14:16:22	ID requested
⏵ 1	2025-09-25 07:19:07	announced

Dataset with its publication pending

submitter keyword: glyoxalase I

ryanodine receptor 2

calcium dysregulation

aging

macaque

prefrontal cortex

hippocampus

proteomics

TuKiet Lam
contact affiliation	Keck MS & Proteomics Resource Yale School of Medicine
contact email	tukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053288
     1. Label: PRIDE project
     2. Name: RyR2-mediated calcium leak increases glyoxalase I in the aging brain