Authors: Thomas Kukar, Meixiang Huang, Erica S Modeste, Eric B Dammer, Christopher J Holler, Qiudong Deng, Georgia L Taylor, Paola Merino, Nicholas T Seyfried
Published: 2020-12-07
DOI: 10.1002/alz.047569
Source: Full article
AbstractBackgroundMutations in the GRN gene, encoding the progranulin (PGRN) protein, are a common cause of Frontotemporal dementia (FTD) and induce haploinsufficiency of PGRN. PGRN is composed of 7.5 repeating domains called granulins (GRNs 1‐7). PGRN is processed into GRNs within the lysosome, where we hypothesize they are critical for lysosome homeostasis and function. However, it is unclear how decreased levels of lysosomal PGRN/GRNs cause FTD, Alzheimer’s disease, and related neurodegenerative disorders.MethodsWe performed quantitative proteomic analysis of whole‐brain tissue from wild‐type (Grn