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The impairment of the respiratory chain or defects in the detoxification system can decrease electron transfer efficiency, reduce ATP production, and increase reactive oxygen species (ROS) production by mitochondria. Accumulation of ROS results in oxidative stress, a hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). β-amyloid has been implicated in the pathogenesis of AD, and...
Aβ 1–42 has been shown to uncouple the mitochondrial respiratory chain and promote the opening of the membrane permeability transition (MPT) pore, leading to cell death. We have previously reported that the spirostenol derivative (22R, 25R)-20α-spirost-5-en-3β-yl hexanoate (SP-233) protects neuronal cells against Aβ 1–42 toxicity by binding to and inactivating the peptide. Picomolar...
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