Differential roles of Aβ processing in hypoxia-induced axonal damage.
Published
Journal Article
Axonopathy is a common and early phase in neurodegenerative and traumatic CNS diseases. Recent work suggests that amyloid β (Aβ) 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 Aβ is a necessary step in structural compromise of retinal ganglion cell (RGC) axons induced by the disease-relevant stressor hypoxia. However, identical blockade of Aβ production was not sufficient to protect axons from associated hypoxia-induced reduction in axonal transport. Thus, Aβ 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.
Full Text
Cited Authors
- Christianson, MG; Lo, DC
Published Date
- May 2015
Published In
Volume / Issue
- 77 /
Start / End Page
- 94 - 105
PubMed ID
- 25771168
Pubmed Central ID
- 25771168
Electronic International Standard Serial Number (EISSN)
- 1095-953X
International Standard Serial Number (ISSN)
- 0969-9961
Digital Object Identifier (DOI)
- 10.1016/j.nbd.2015.02.027
Language
- eng