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PXD035889 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDeficiency of the frontotemporal dementia gene GRN results in gangliosidosis
DescriptionHaploinsufficiency 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSebastian Boland
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-08 09:52:40ID requested
12022-09-18 09:30:23announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: haploinsufficiency,frontotemporal dementia, gangliosides,BMP,PGRN, lysosome
Contact List
J. Wade Harper
contact affiliationDepartment of Cell Biology Harvard Medical School Boston, MA USA
contact emailwade_harper@hms.harvard.edu
lab head
Sebastian Boland
contact affiliationHarvard T.H. Chan School of Public Health Harvard Medical School
contact emailsboland@hsph.harvard.edu
dataset submitter
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Dataset FTP location
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