2021年8月3日 · We have shown that in addition to CTSL and CTSB, multiple proteases can process PGRN and liberate granulins, and all of these proteases act in a pH-dependent manner.

2017年8月23日 · Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. PGRN is localized to the lysosome and important for proper lysosome function. However, the metabolism of PGRN in the lysosome is still unclear.

2022年2月4日 · Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN is comprised of 7.5 granulin repeats and is processed into individual granulin peptides in the lysosome. However, very little is known about the levels and regulations of individual granulin peptides due to the lack of specific antibodies.

2017年1月10日 · Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis.

2017年1月12日 · 分泌的PGRN通过sortilin或不依赖阳离子的甘露糖6-磷酸受体掺入细胞，并促进了溶酶体的酸化和CTSDmat的降解。 此外，PGRN水平的变化导致不溶性TDP-43的细胞类型特异性增加。

2020年12月7日 · Compared to healthy volunteers, AL001 treatment rescued cathepsin B (CTSB), a marker of lysosomal function, by 58%. AL001 treatment also partially normalized markers of inflammation and gliosis, osteopontin (SPP1) and chitotriosidase (CHIT1) by …

2020年8月31日 · Dominant mutations in the human progranulin (GRN) gene drastically reduce progranulin (PGRN) protein levels and are a major cause of familial forms of frontotemporal lobar degeneration (FTLD)...

2021年8月1日 · We confirmed the role of cathepsin B and cathepsin L in PGRN processing and showed that these and several previously unidentified lysosomal proteases (cathepsins E, G, K, S and V) are able to...

2019年3月26日 · In fact, we found for the first time that the down-regulation and inhibition of a lysozyme Cathepsin B (CTSB) increases PGRN levels (Tanaka et al. 2017). On the other hand, the following studies clearly showed that Cathepsin L (CTSL) mediates the processing of PGRN into GRN peptides in lysosomes (Holler et al. 2017, Lee et al. 2017, Zhou et al ...

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 …