Amyloid Precursor Protein Mediates Neuronal Protection from Rotenone Toxicity
Kathryn Cimdins, Hayley S Waugh, Vicki Chrysostomou, M Isabel G Lopez Sanchez, Vanessa A Johannsen, Mark J Cook, Jonathan G Crowston, Andrew F Hill, James A Duce, Ashley I Bush, Ian A Trounce
MOLECULAR NEUROBIOLOGY | SPRINGER | Published : 2019
Mitochondrial complex I dysfunction is the most common respiratory chain defect in human disorders and a hotspot for neurodegenerative diseases. Amyloid precursor protein (APP) and its non-amyloidogenic processing products, in particular soluble APP α (sAPPα), have been shown to provide neuroprotection in models of neuronal injury; however, APP-mediated protection from acute mitochondrial injury has not been previously reported. Here, we use the plant-derived pesticide rotenone, a potent complex I-specific mitochondrial inhibitor, to discover neuroprotective effects of APP and sAPPα in vitro, in neuronal cell lines over-expressing APP, and in vivo, in a retinal neuronal rotenone toxicity mou..View full abstract
Awarded by BrightFocus Foundation Thomas R. Lee award
This research was supported by the BrightFocus Foundation Thomas R. Lee award (G2009020), the DHB Foundation (IAT) and the Mason Foundation (IAT and JAD). CERA receives Operational Infrastructure Support from the Victorian Government, Australia.