2023年11月16日 · We found that PGRN loss impairs the lysosome’s degradative capacity with increased levels of v-ATPase subunits on the lysosome membrane, increased hydrolases within the lysosome, altered protein regulations related to …

2013年10月10日 · PGRN was colocalized with Lamp1, a lysosomal marker, and Lamp1-positive areas in GRN-deficient (KO) mice were significantly expanded compared with wild-type (WT) mice after TBI.

RagC and PGRN are lysosome proteins that coenrich with LAMP1 at amyloid plaques. (A) WT and 5xFAD cerebral cortices stained for RagC and LAMP showing colocalization of the two proteins in neuronal cell bodies and around plaques.

2016年5月5日 · Using confocal microscopy and fluorescent signal intensity plots of PGRN and markers for early endosomes (Rab5), late endosomes (Rab7), trans -Golgi network (Sortilin), and early lysosomes (Lamp1), we showed that PGRN did not co-localize with Rab5 + vesicles in Grn+/+ microglia (data not shown), but was detected in Golgi apparatus and in ...

2017年1月10日 · We firstly confirmed PGRN expression in these cells and its co-localization with Lamp1, a lysosome marker (Fig. 1A and B) . Then, we investigated whether PGRN expression increases in these cells exposed to lysosome alkalizers.

2022年6月30日 · Progranulin (PGRN) haploinsufficiency from autosomal dominant mutations in the PGRN gene causes frontotemporal lobar degeneration, which is characterized by cytoplasmic inclusions predominantly containing TDP-43 (FTLD-TDP).

Progranulin deficiency leads to decreased levels of human APP and Aβ in a sex- and age-dependent manner and enhanced inflammatory and lysosomal responses in the plaque-associated microglia. Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD).

Microglial PGRN deficiency induces diet-dependent alterations in hypothalamic lysosomes. (A) Representative images and quantification of Lamp1 + lysosome mass in the ARH, specifically in Iba1 + microglia and β-endorphin + POMC neurons of GrnWT and GrnMGKO male mice fed an NCD or HFD for 10 weeks (n = 3 mice per group). Approximately 100 cells per mouse were analyzed. Scale bars, 20 μm. (B ...

2023年7月15日 · To better understand the role of PGRN in regulating lysosome function, this study examined how loss of GRN impacts total LAMP1 protein expression and cathepsin activities.

2022年1月4日 · Significant colocalization between PGRN and the lysosomal marker LAMP1 was observed in both Psap−/− and Psap−/− Sort−/− microglia (Fig. 4A), indicating that there exists additional PSAP and sortilin independent PGRN lysosome trafficking mechanism in microglia.