| First Author | Oh Y | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 18 | PubMed ID | 36142484 |
| Mgi Jnum | J:329306 | Mgi Id | MGI:7342918 |
| Doi | 10.3390/ijms231810563 | Citation | Oh Y, et al. (2022) SPIN90 Deficiency Ameliorates Amyloid beta Accumulation by Regulating APP Trafficking in AD Model Mice. Int J Mol Sci 23(18) |
| abstractText | Alzheimer's disease (AD), a common form of dementia, is caused in part by the aggregation and accumulation in the brain of amyloid beta (Abeta), a product of the proteolytic cleavage of amyloid precursor protein (APP) in endosomes. Trafficking of APP, such as surface-intracellular recycling, is an early critical step required for Abeta generation. Less is known, however, about the molecular mechanism regulating APP trafficking. This study investigated the mechanism by which SPIN90, along with Rab11, modulates APP trafficking, Abeta motility and accumulation, and synaptic functionality. Brain Abeta deposition was lower in the progeny of 5xFAD-SPIN90KO mice than in 5xFAD-SPIN90WT mice. Analysis of APP distribution and trafficking showed that the surface fraction of APP was locally distinct in axons and dendrites, with these distributions differing significantly in 5xFAD-SPIN90WT and 5xFAD-SPIN90KO mice, and that neural activity-driven APP trafficking to the surface and intracellular recycling were more actively mobilized in 5xFAD-SPIN90KO neurons. In addition, SPIN90 was found to be cotrafficked with APP via axons, with ablation of SPIN90 reducing the intracellular accumulation of APP in axons. Finally, synaptic transmission was restored over time in 5xFAD-SPIN90KO but not in 5xFAD-SPIN90WT neurons, suggesting SPIN90 is implicated in Abeta production through the regulation of APP trafficking. |
