Abstract
Mitochondrial dysfunction plays a key role in the progression of Alzheimer’s disease (AD). The accumulation of amyloid-beta peptide (Aβ) in the brains of AD patients is thought to be closely related to neuronal mitochondrial dysfunction and oxidative stress. Therefore, protecting mitochondria from Aβ-induced neurotoxicity is an effective strategy for AD therapeutics. In a previous study, we found that geniposide, a pharmacologically active compound purified from gardenia fruit, has protective effects on oxidative stress and mitochondrial dysfunction in AD transgenic mouse models. However, whether geniposide has a protective effect on Aβ-induced neuronal dysfunction remains unknown. In the present study, we demonstrate that geniposide protects cultured primary cortical neurons from Aβ-mediated mitochondrial dysfunction by recovering ATP generation, mitochondrial membrane potential (MMP), and cytochrome c oxidase (CcO) and caspase 3/9 activity; by reducing ROS production and cytochrome c leakage; as well as by inhibiting apoptosis. These findings suggest that geniposide may attenuate Aβ-induced neuronal injury by inhibiting mitochondrial dysfunction and oxidative stress.
Highlights
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the clinical manifestation of severe memory impairment, cognitive deficits and personality changes [1,2,3,4,5]
By cultured primary cortical neurons, we investigated the effects of geniposide on oligomeric Aβ-induced mitochondrial dysfunction related to neurotoxicity and apoptosis
The neurons were treated with various concentrations (1.25, 2.5, 5, 10, and 20 μM) of geniposide for 24 h to determine whether geniposide is toxic to neurons
Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the clinical manifestation of severe memory impairment, cognitive deficits and personality changes [1,2,3,4,5]. The pathologic characteristics of AD are amyloid-beta peptide (Aβ) deposition, neurofibrillary tangle (NFT) formation and neuronal loss [6, 7].
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