PXD021773-1

PXD021773 is an original dataset announced via ProteomeXchange.

Title	Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow
Description	Cell-to-cell communications are critical determinants of pathophysiological phenotypes, but methodologies for their systematic elucidation are lacking. Herein, we propose an approach for the Systematic Elucidation and Assessment of Regulatory Cell-to-cell Interaction Networks (SEARCHIN) to elucidate ligand-mediated interactions between distinct cellular compartments. To test this approach, we selected a model of amyotrophic lateral sclerosis (ALS), in which astrocytes expressing mutant superoxide dismutase-1 (mutSOD1) kill wild-type motor neurons (MNs) by an unknown mechanism. Integrative analysis that combines proteomics and regulatory network analysis infers the interaction between astrocyte-released amyloid precursor protein (APP) and death receptor-6 (DR6) on MNs as the top predicted ligand-receptor pair. The inferred deleterious role of APP and DR6 is confirmed in vitro in models of ALS. Moreover, the DR6 knockdown in MNs of transgenic mutSOD1 mice attenuates the ALS-like phenotype. Our results support the usefulness of integrative, systems biology approach to gain insights into complex neurobiological disease processes as in ALS and posit that the proposed methodology is not restricted to this biological context and could be used in a variety of other non-cell-autonomous communication mechanisms.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_08:56:58.067.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Rattus rattus (Black rat); NCBI TaxID: 10117;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-01 00:15:20	ID requested
⏵ 1	2021-09-09 08:56:58	announced

Mishra V, Re DB, Le Verche V, Alvarez MJ, Vasciaveo A, Jacquier A, Doulias PT, Greco TM, Nizzardo M, Papadimitriou D, Nagata T, Rinchetti P, Perez-Torres EJ, Politi KA, Ikiz B, Clare K, Than ME, Corti S, Ischiropoulos H, Lotti F, Califano A, Przedborski S, Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow. Nat Commun, 11(1):5579(2020) [pubmed]

submitter keyword: SEARCHIN, ALS, motor neuron, death receptor-6, mutant SOD1, non-cell autonomous, Bioinformatics

Serge Przedborski
contact affiliation	Page and William Black Professor of Neurology Vice-Chair, Research Chief, Movement Disorders Division Director, Columbia Translational Neuroscience Initiative Co-Director, Center for Motor Neuron Biology and Disease Co-Director, Thompson Family Foundation Initiativ Departments of Neurology, Pathology & Cell Biology and Neuroscience College of Physicians and Surgeons, Room 5-420 630 West 168th Street Columbia University New York, NY 10032 Phone: 212-342-4119 Fax: 212-342-4512
contact email	sp30@cumc.columbia.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.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/2021/09/PXD021773

PRIDE project URI

• PRIDE
  1. PXD021773
     1. Label: PRIDE project
     2. Name: Systematic elucidation of neuron-astrocyte interaction in models of amyotrophic lateral sclerosis using multi-modal integrated bioinformatics workflow