PXD035889

PXD035889 is an original dataset announced via ProteomeXchange.

Title	Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis
Description	Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.
HostingRepository	PRIDE
AnnounceDate	2022-09-18
AnnouncementXML	Submission_2022-09-18_09:30:22.732.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Boland
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	2022-08-08 09:52:40	ID requested
⏵ 1	2022-09-18 09:30:23	announced

Dataset with its publication pending

submitter keyword: haploinsufficiency,frontotemporal dementia, gangliosides,BMP,PGRN, lysosome

J. Wade Harper
contact affiliation	Department of Cell Biology Harvard Medical School Boston, MA USA
contact email	wade_harper@hms.harvard.edu
lab head
Sebastian Boland
contact affiliation	Harvard T.H. Chan School of Public Health Harvard Medical School
contact email	sboland@hsph.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035889
     1. Label: PRIDE project
     2. Name: Deficiency of the frontotemporal dementia gene GRN results in gangliosidosis