PXD075747

PXD075747 is an original dataset announced via ProteomeXchange.

Title	Small Molecule Guided Small Molecule Guided Photocatalytic Proteomics Profiling of Amyloid Deposits in Hippocampal and Cortical Alzheimer’s Disease TissuesPhotocatalytic Proteomics Profiling of Amyloid Deposits in Hippocampal and Cortical Alzheimer’s Disease Tissues
Description	he spatiotemporal progression of amyloid pathology in Alzheimer's disease (AD) follows a characteristic pattern, spreading from the cortex to the hippocampus brain regions. However, analytical methods for comparative profiling of amyloid plaque composition between these two regions are limited. Herein, we developed a small molecule guided method to selectively label, enrich, profile and compare amyloid interactome in cortical and hippocampal regions of AD brain tissue. We embarked on rational design of probes to transform Congo Red derivatives from amyloid chromophore to singlet fluorescent sensor, and finally to triplet photocatalytic labeling probe. While retaining the amyloid binding selectivity, P5 outperformed other probes in photocatalytic labeling of recombinant amyloid proteins and amyloid deposits from AD mouse brain tissues. We applied P5 to selectively labeling and enrichment of amyloid plaques in hippocampus and cortex, respectively. The robustness of our methodology was confirmed by the consistent identification of established AD biomarkers (e.g. APP, ApoE) in both regions. Subsequent comparative proteomics not only demonstrated the critical involvement of the mitophagy-lysosome axis in AD pathogenesis, but also uncovered a previously unrecognized region-specific functional divergence. Proteomic profiles distinguished that AD’s cortex primarily involves upstream mitophagy, whereas AD’s hippocampus actively triggers downstream lysosomal degradation. Overall, we report a small-molecule-based photocatalytic proteomic profiling method to resolve amyloid deposits and elucidate their region-specific interactome heterogeneity.
HostingRepository	PRIDE
AnnounceDate	2026-03-18
AnnouncementXML	Submission_2026-03-17_18:30:21.069.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jing Yan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-17 05:52:44	ID requested
⏵ 1	2026-03-17 18:30:21	announced

Dataset with its publication pending

submitter keyword: amyloid, proximity labeling, Alzheimer's disease,chemical proteomics, photosensitizer

Jing Yan
contact affiliation	Research Center, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
contact email	yanj05@dmu.edu.cn
lab head
Jing Yan
contact affiliation	大连医科大学
contact email	yanj05@dmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD075747
     1. Label: PRIDE project
     2. Name: Small Molecule Guided Small Molecule Guided Photocatalytic Proteomics Profiling of Amyloid Deposits in Hippocampal and Cortical Alzheimer’s Disease TissuesPhotocatalytic Proteomics Profiling of Amyloid Deposits in Hippocampal and Cortical Alzheimer’s Disease Tissues