PXD059089-1

PXD059089 is an original dataset announced via ProteomeXchange.

Title	Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease
Description	Aging is the most prominent risk factor for Alzheimer's disease (AD). However, the cellular mechanisms linking neuronal proteostasis decline to the characteristic aberrant protein deposits in AD brains remain elusive. Here, we develop transdifferentiated neurons (tNeurons) from 5 human dermal fibroblasts as a neuronal model that retains aging hallmarks and exhibits ADlinked vulnerabilities. Remarkably, AD tNeurons accumulate proteotoxic deposits, including phospho-Tau and Aβ, resembling those in AD patient and APP mouse brains. Quantitative tNeurons proteomics identify aging and AD-linked deficits in proteostasis and organelle homeostasis, most notably in endosome-lysosomal components. Lysosomal deficits in aged 10 tNeurons, including constitutive lysosomal damage and ESCRT-mediated lysosomal repair defects, are exacerbated in AD tNeurons and linked to inflammatory cytokine secretion and cell death. Supporting lysosomal deficits’ centrality in AD, compounds ameliorating lysosomal function reduce Aβ deposits and cytokine secretion. Thus, the tNeuron model system reveals impaired lysosomal homeostasis as an early event of aging and AD.
HostingRepository	PRIDE
AnnounceDate	2024-12-20
AnnouncementXML	Submission_2024-12-20_04:03:54.783.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Miguel Prado
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-20 03:58:20	ID requested
⏵ 1	2024-12-20 04:03:55	announced

Dataset with its publication pending

submitter keyword: Proteostasis, lysosome, Alzheimer, Neurons

Miguel A. Prado
contact affiliation	Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
contact email	miguel.prado@ispasturias.es
lab head
Miguel Prado
contact affiliation	Harvard Medical School, Boston, USA Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain (lab head)
contact email	miguel.prado@ispasturias.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/12/PXD059089

PRIDE project URI

• PRIDE
  1. PXD059089
     1. Label: PRIDE project
     2. Name: Proteostasis and lysosomal repair deficits in transdifferentiated neurons of Alzheimer's disease