PXD044647

PXD044647 is an original dataset announced via ProteomeXchange.

Title	Neural and Metabolic Dysregulation in PMM2 deficient human in vitro neural models
Description	PMM2-CDG is a rare inborn error of metabolism caused by deficiency of the phosphomannomutase (PMM2) enzyme, which leads to impaired protein glycosylation. While the disorder presents primarily with neurological symptoms, there is limited knowledge about the specific brain-related changes that result from PMM deficiency. We found aberrant neural activity in 2D neuronal networks from individuals with PMM2-CDG. Multi-omics datasets from 3D brain organoids derived from individuals with PMM2-CDG revealed widespread decrease in protein glycosylation, highlighting impaired glycosylation as a key pathological feature of PMM2-CDG. Further, we identified impaired mitochondrial structure and abnormal glucose metabolism in PMM2-CDG organoids indicating disturbances in energy metabolism. Correlation between PMM2 enzymatic activity in brain organoids and symptom severity suggests that the level of PMM2 enzyme function directly influences neurological manifestations. These findings enhance our understanding of specific brain-related perturbations associated with PMM2-CDG, offering insights into the underlying mechanisms and potential directions for therapeutic interventions.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:24.236.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Akhilesh Pandey
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-18 08:42:44	ID requested
1	2024-04-25 12:49:06	announced
⏵ 2	2024-10-22 06:37:24	announced	2024-10-22: Updated project metadata.

10.1016/J.CELREP.2024.113883;

submitter keyword: disease model, neurodevelopmental disorder,Phosphomannomutase-2, iPSC-derived neurons, congenital disorder of glycosylation, stem cells, brain organoids

Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology Mayo Clinic, Rochester, Minnesota 55905 United States
contact email	pandey.akhilesh@mayo.edu
lab head
Akhilesh Pandey
contact affiliation	Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905
contact email	pandey.akhilesh@mayo.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/2024/04/PXD044647

PRIDE project URI

• PRIDE
  1. PXD044647
     1. Label: PRIDE project
     2. Name: Neural and Metabolic Dysregulation in PMM2 deficient human in vitro neural models