Network analysis of the progranulin-deficient mouse brain proteome reveals pathogenic mechanisms shared in human frontotemporal dementia caused by GRN mutations.
Frontotemporal dementia (FTD)
Frontotemporal lobar degeneration (FTLD)
GPNMB
Galectin-3
Inflammation
Lysosome
Neurodegeneration
Progranulin (PGRN)
Proteomics
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
07 10 2020
07 10 2020
Historique:
received:
10
09
2020
accepted:
13
09
2020
entrez:
8
10
2020
pubmed:
9
10
2020
medline:
1
6
2021
Statut:
epublish
Résumé
Heterozygous, loss-of-function mutations in the granulin gene (GRN) encoding progranulin (PGRN) are a common cause of frontotemporal dementia (FTD). Homozygous GRN mutations cause neuronal ceroid lipofuscinosis-11 (CLN11), a lysosome storage disease. PGRN is a secreted glycoprotein that can be proteolytically cleaved into seven bioactive 6 kDa granulins. However, it is unclear how deficiency of PGRN and granulins causes neurodegeneration. To gain insight into the mechanisms of FTD pathogenesis, we utilized Tandem Mass Tag isobaric labeling mass spectrometry to perform an unbiased quantitative proteomic analysis of whole-brain tissue from wild type (Grn
Identifiants
pubmed: 33028409
doi: 10.1186/s40478-020-01037-x
pii: 10.1186/s40478-020-01037-x
pmc: PMC7541308
doi:
Substances chimiques
GRN protein, human
0
Grn protein, mouse
0
Progranulins
0
Proteome
0
Tpp1 protein, mouse
0
Tripeptidyl-Peptidase 1
0
TPP1 protein, human
EC 3.4.14.9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
163Subventions
Organisme : NINDS NIH HHS
ID : R01 NS105971
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066511
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS093362
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG045390
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092089
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS055077
Pays : United States
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