PXD053992

PXD053992 is an original dataset announced via ProteomeXchange.

Title	A protective role for APP in nuclear waste clearance via lysosomal exocytosis
Description	Amyloid precursor protein (APP) is widely known for its role in Alzheimer’s disease (AD) pathogenesis through its proteolytic processing into amyloid-β peptides. However, its physiological function remains incompletely understood. Here, we uncover a protective role for full-length APP in facilitating the disposal of nuclear-derived debris under genotoxic stress. In both cultured cells and in vivo mouse models, loss of APP leads to nuclear waste accumulation, increased inflammation, and cell death, whereas APP overexpression mitigates these effects. Mechanistically, we show that APP supports the extracellular release of nuclear material through lysosomal exocytosis. APP mutants associated with familial AD fail to mediate this process. Consistently, human AD brain tissue exhibits abnormal nuclear morphology, accumulation of nuclear waste in the cytoplasm, and reduced APP levels per neuron. These findings highlight a conserved cellular mechanism by which APP contributes to nuclear and cellular homeostasis, and suggest that impaired nuclear waste clearance may represent an underappreciated contributor to neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2026-06-12
AnnouncementXML	Submission_2026-06-11_16:07:06.784.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Godfried Dougnon
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-16 20:08:13	ID requested
⏵ 1	2026-06-11 16:07:07	announced

10.1073/PNAS.2524190123;

submitter keyword: extracellular waste, Alzheimer's disease, nucleus, neurodegeneration,Amyloid precursor protein

Hideaki Matsui
contact affiliation	Department of Neuroscience of Disease, Brain Research Institute, Niigata University
contact email	hide0729.bri@niigata-u.ac.jp
lab head
Godfried Dougnon
contact affiliation	Niigata University
contact email	dougnong@bri.niigata-u.ac.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053992
     1. Label: PRIDE project
     2. Name: A protective role for APP in nuclear waste clearance via lysosomal exocytosis