PXD041095

PXD041095 is an original dataset announced via ProteomeXchange.

Title	Granulins rescue inflammation, lysosome dysfunction, and neuropathology in a mouse model of progranulin deficiency
Description	In this study, we investigate whether individual granulin subunits derived from the precursor protein progranulin are beneficial. We test this by asking if delivery of a single granulin to the brains of a preclinical model of FTD-GRN Grn-/-mice is sufficient to ameliorate disease-like phenotypes. We performed intracerebroventricular injections of recombinant adeno-associated virus (rAAV2/1) encoding granulin-2, granulin-4, full-length PGRN or GFP in neonatal Grn+/+ and Grn-/- mice. Following AAV injections, mice were aged for 12 months, tissues collected, and analyzed. Quantitative proteomics of the thalamus identified lysosomal function and neuroinflammation as pathways ameliorated by the expression of granulins. Biochemical markers of lysosomal dysfunction, neuroinflammation, and disease-like pathology were assessed via immunoblot and immunohistochemistry. We found that both granulin-2 and granulin-4 rescue markers of lysosomal dysfunction and neuroinflammation in cortical, hippocampal, and thalamic tissue.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:01:58.996.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-24 05:21:00	ID requested
1	2024-10-14 17:28:22	announced
⏵ 2	2024-10-22 07:01:59	announced	2024-10-22: Updated project metadata.

submitter keyword: Lipofuscin, CD68, Neurodegeneration, Inflammation,Progranulin (PGRN), BMP, Adeno-associated virus, Frontotemporal dementia (FTD), Lysosome, Galectin-3, Lipidomics, Granulins, Proteomics

Thomas Kukar
contact affiliation	Pharmocology Asc Professor Emory University
contact email	tkukar@emory.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041095
     1. Label: PRIDE project
     2. Name: Granulins rescue inflammation, lysosome dysfunction, and neuropathology in a mouse model of progranulin deficiency