| First Author | Du H | Year | 2021 |
| Journal | Life Sci Alliance | Volume | 4 |
| Issue | 7 | PubMed ID | 34103390 |
| Mgi Jnum | J:308451 | Mgi Id | MGI:6729558 |
| Doi | 10.26508/lsa.202000874 | Citation | Du H, et al. (2021) A multifaceted role of progranulin in regulating amyloid-beta dynamics and responses. Life Sci Alliance 4(7) |
| abstractText | Haploinsufficiency of progranulin (PGRN) is a leading cause of frontotemporal lobar degeneration (FTLD). PGRN polymorphisms are associated with Alzheimer's disease. PGRN is highly expressed in the microglia near Abeta plaques and influences plaque dynamics and microglial activation. However, the detailed mechanisms remain elusive. Here we report that PGRN deficiency reduces human APP and Abeta levels in the young male but not female mice. PGRN-deficient microglia exhibit increased expression of markers associated with microglial activation, including CD68, galectin-3, TREM2, and GPNMB, specifically near Abeta plaques. In addition, PGRN loss leads to up-regulation of lysosome proteins and an increase in the nuclear localization of TFE3, a transcription factor involved in lysosome biogenesis. Cultured PGRN-deficient microglia show enhanced nuclear translocation of TFE3 and inflammation in response to Abeta fibril treatment. Taken together, our data revealed a sex- and age-dependent effect of PGRN on APP metabolism and a role of PGRN in regulating lysosomal activities and inflammation in plaque-associated microglia. |
