Submitted by hscelsi3 on July 9, 2020 - 3:34pm
| Title | Progranulin deficiency leads to reduced glucocerebrosidase activity. |
| Publication Type | Journal Article |
| Year of Publication | 2019 |
| Authors | Zhou, X, Paushter, DH, Pagan, MD, Kim, D, Santos, MNunez, Lieberman, RL, Overkleeft, HS, Sun, Y, Smolka, MB, Hu, F |
| Journal | PLoS One |
| Volume | 14 |
| Issue | 7 |
| Pagination | e0212382 |
| Date Published | 2019 |
| ISSN | 1932-6203 |
| Keywords | Animals, Cell Line, Disease Models, Animal, Female, Frontotemporal Lobar Degeneration, Glucosylceramidase, Haploinsufficiency, HEK293 Cells, Humans, Lysosomes, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Neuronal Ceroid-Lipofuscinoses, Progranulins, Recombinant Proteins |
| Abstract | Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GCase), and is essential for proper GCase activity. GCase activity is significantly reduced in tissue lysates from PGRN-deficient mice. This is further evidence that reduced lysosomal hydrolase activity may be a pathological mechanism in cases of GRN-related FTLD and NCL. |
| DOI | 10.1371/journal.pone.0212382 |
| Alternate Journal | PLoS ONE |
| PubMed ID | 31291241 |
| PubMed Central ID | PMC6619604 |
| Grant List | F32 AG027647 / AG / NIA NIH HHS / United States R01 NS088448 / NS / NINDS NIH HHS / United States R01 NS095954 / NS / NINDS NIH HHS / United States |
