| First Author | Son SM | Year | 2015 |
| Journal | Neurobiol Aging | Volume | 36 |
| Issue | 12 | Pages | 3214-3227 |
| PubMed ID | 26452999 | Mgi Jnum | J:232372 |
| Mgi Id | MGI:5776668 | Doi | 10.1016/j.neurobiolaging.2015.09.005 |
| Citation | Son SM, et al. (2015) Thrombospondin-1 prevents amyloid beta-mediated synaptic pathology in Alzheimer's disease. Neurobiol Aging 36(12):3214-3227 |
| abstractText | Alzheimer's disease (AD) is characterized by impaired cognitive function and memory loss, which are often the result of synaptic pathology. Thrombospondin (TSP) is an astrocyte-secreted protein, well known for its function as a modulator of synaptogenesis and neurogenesis. Here, we investigated the effects of TSP-1 on AD pathogenesis. We found that the level of TSP-1 expression was decreased in AD brains. When we treated astrocytes with amyloid beta (Abeta), secreted TSP-1 was decreased in autophagy-dependent manner. In addition, treatment with Abeta induced synaptic pathology, such as decreased dendritic spine density and reduced synaptic activity. These effects were prevented by coincubation of TSP-1 with Abeta, which acts through the TSP-1 receptor alpha-2-delta-1 in neurons. Finally, intrasubicular injection with TSP-1 into AD model mouse brains mitigated the Abeta-mediated reduction of synaptic proteins and related signaling pathways. These results indicate that TSP-1 is a potential therapeutic target in AD pathogenesis. |
