PXD031091

PXD031091 is an original dataset announced via ProteomeXchange.

Title	NGLY1 mutations cause protein aggregation in human neurons
Description	Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy and seizures. NGLY1’s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons, but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.
HostingRepository	PRIDE
AnnounceDate	2024-06-16
AnnouncementXML	Submission_2024-06-15_22:55:52.857.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD031091
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jolene Diedrich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-19 09:26:46	ID requested
⏵ 1	2024-06-15 22:55:53	announced

10.1016/j.celrep.2023.113466;

10.6019/PXD031091;

Manole A, Wong T, Rhee A, Novak S, Chin SM, Tsimring K, Paucar A, Williams A, Newmeyer TF, Schafer ST, Rosh I, Kaushik S, Hoffman R, Chen S, Wang G, Snyder M, Cuervo AM, Andrade L, Manor U, Lee K, Jones JR, Stern S, Marchetto MC, Gage FH, NGLY1 mutations cause protein aggregation in human neurons. Cell Rep, 42(12):113466(2023) [pubmed]

submitter keyword: forebrain organoids, fragmented mitochondria, heat shock proteins, protein aggregates,NGLY1 deficiency, neural cells

Fred H Gage
contact affiliation	Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
contact email	gage@salk.edu
lab head
Jolene Diedrich
contact affiliation	Salk
contact email	jdiedrich@salk.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/2024/05/PXD031091

PRIDE project URI

• PRIDE
  1. PXD031091
     1. Label: PRIDE project
     2. Name: NGLY1 mutations cause protein aggregation in human neurons