| First Author | Guan Z | Year | 2020 |
| Journal | Front Cell Neurosci | Volume | 14 |
| Pages | 260 | PubMed ID | 32973454 |
| Mgi Jnum | J:311250 | Mgi Id | MGI:6752170 |
| Doi | 10.3389/fncel.2020.00260 | Citation | Guan Z, et al. (2020) Progranulin Administration Attenuates beta-Amyloid Deposition in the Hippocampus of 5xFAD Mice Through Modulating BACE1 Expression and Microglial Phagocytosis. Front Cell Neurosci 14:260 |
| abstractText | Loss of function mutations in the progranulin (PGRN) gene is a risk factor for Alzheimer's disease (AD). Previous works reported that the deficiency of PGRN accelerates beta-amyloid (Abeta) accumulation in AD transgenic mouse brains while overexpression of PGRN could restrain disease progression. However, mechanisms of PGRN in protecting against Abeta deposition remains unclear. Here, using the 5xFAD AD mouse model, we show that intrahippocampal injection of PGRN protein leads to a reduction of Abeta plaques, downregulation of beta-secretase 1 (BACE1), and enhanced microglia Abeta phagocytosis in the mouse hippocampus. Furthermore, PGRN treatment inhibited BACE1 expression in N2a cells and primary culture neurons and improved the phagocytic capacity of microglia isolated from 5xFAD mouse brains. Collectively, our results provide further evidence that enhancing progranulin could be a promising option for AD therapy. |
