PXD044093-1

PXD044093 is an original dataset announced via ProteomeXchange.

Title	SORL1 regulates APOE and CLU levels in human neurons
Description	SORL1 is implicated in the pathogenesis of Alzheimer’s disease (AD) through genetic studies. To interrogate the role(s) of SORL1 in human brain cells, SORL1 null iPSCs are differentiated to neuron, astrocyte, microglial, and endothelial cell fates. Loss of SORL1 leads to alterations in both overlapping and distinct pathways across cell types, with the greatest effects in neurons and astrocytes. SORL1 loss induces a neuron-specific reduction in APOE and CLU and altered lipid profiles. Enhancement of retromer-mediated trafficking rescues tau phenotypes observed in SORL1 null neurons but does not rescue APOE levels. Pathway analyses implicate TGF-β/SMAD signaling in SORL1 function, and modulating SMAD signaling in neurons alters APOE RNA levels in a SORL1-dependent manner. Analyses of iPSCs derived from a large cohort reveal a neuron-specific association between SORL1, APOE, and CLU levels, a finding validated in post-mortem brain. These studies provide a mechanistic link between strong genetic risk factors for AD.
HostingRepository	PRIDE
AnnounceDate	2023-10-24
AnnouncementXML	Submission_2023-10-24_09:58:22.500.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	DucDuong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-25 20:49:31	ID requested
⏵ 1	2023-10-24 09:58:23	announced
2	2023-11-14 09:06:33	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:07:39	announced	2024-10-22: Updated project metadata.

Lee H, Aylward AJ, Pearse RV, Lish AM, Hsieh YC, Augur ZM, Benoit CR, Chou V, Knupp A, Pan C, Goberdhan S, Duong DM, Seyfried NT, Bennett DA, Taga MF, Huynh K, Arnold M, Meikle PJ, De Jager PL, Menon V, Young JE, Young-Pearse TL, Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1. Cell Rep, 42(8):112994(2023) [pubmed]

submitter keyword: LC-MS/MS, Alzheimer's, TMT

TracyYoung-Pearse
contact affiliation	Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
contact email	tpearse@bwh.harvard.edu
lab head
DucDuong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
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/2023/10/PXD044093

PRIDE project URI

• PRIDE
  1. PXD044093
     1. Label: PRIDE project
     2. Name: SORL1 regulates APOE and CLU levels in human neurons