| First Author | Christianson MG | Year | 2015 |
| Journal | Neurobiol Dis | Volume | 77 |
| Pages | 94-105 | PubMed ID | 25771168 |
| Mgi Jnum | J:258954 | Mgi Id | MGI:6140412 |
| Doi | 10.1016/j.nbd.2015.02.027 | Citation | Christianson MG, et al. (2015) Differential roles of Abeta processing in hypoxia-induced axonal damage. Neurobiol Dis 77:94-105 |
| abstractText | Axonopathy is a common and early phase in neurodegenerative and traumatic CNS diseases. Recent work suggests that amyloid beta (Abeta) produced from amyloid precursor protein (APP) may be a critical downstream mediator of CNS axonopathy in CNS diseases, particularly those associated with hypoxia. We critically tested this hypothesis in an adult retinal explant system that preserves the three-dimensional organization of the retina while permitting direct imaging of two cardinal features of early-stage axonopathy: axonal structural integrity and axonal transport capacity. Using this system, we found via pharmacological inhibition and genetic deletion of APP that production of Abeta is a necessary step in structural compromise of retinal ganglion cell (RGC) axons induced by the disease-relevant stressor hypoxia. However, identical blockade of Abeta production was not sufficient to protect axons from associated hypoxia-induced reduction in axonal transport. Thus, Abeta mediates distinct facets of hypoxia-induced axonopathy and may represent a functionally selective pharmacological target for therapies directed against early-stage axonopathy in CNS diseases. |
