| First Author | Heckmann BL | Year | 2019 |
| Journal | Cell | Volume | 178 |
| Issue | 3 | Pages | 536-551.e14 |
| PubMed ID | 31257024 | Mgi Jnum | J:278330 |
| Mgi Id | MGI:6342645 | Doi | 10.1016/j.cell.2019.05.056 |
| Citation | Heckmann BL, et al. (2019) LC3-Associated Endocytosis Facilitates beta-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer's Disease. Cell 178(3):536-551.e14 |
| abstractText | The expression of some proteins in the autophagy pathway declines with age, which may impact neurodegeneration in diseases, including Alzheimer's Disease. We have identified a novel non-canonical function of several autophagy proteins in the conjugation of LC3 to Rab5(+), clathrin(+) endosomes containing beta-amyloid in a process of LC3-associated endocytosis (LANDO). We found that LANDO in microglia is a critical regulator of immune-mediated aggregate removal and microglial activation in a murine model of AD. Mice lacking LANDO but not canonical autophagy in the myeloid compartment or specifically in microglia have a robust increase in pro-inflammatory cytokine production in the hippocampus and increased levels of neurotoxic beta-amyloid. This inflammation and beta-amyloid deposition were associated with reactive microgliosis and tau hyperphosphorylation. LANDO-deficient AD mice displayed accelerated neurodegeneration, impaired neuronal signaling, and memory deficits. Our data support a protective role for LANDO in microglia in neurodegenerative pathologies resulting from beta-amyloid deposition. |
