Journal article

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

Abstract

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..

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