Abstract
Alzheimer′s disease (AD) is a fatal neurodegenerative disease. Brain amyloid-β deposition is a crucial feature of AD, causing neuronal cell death by inducing oxidative damage. Reactive oxygen species (ROS) activate NF-κB, which induces expression of Nucling. Nucling is a pro-apoptotic factor recruiting the apoptosome complex. Lycopene is an antioxidant protecting from oxidative stress-induced cell damage. We investigated whether lycopene inhibits amyloid-β-stimulated apoptosis through reducing ROS and inhibiting mitochondrial dysfunction and NF-κB-mediated Nucling expression in neuronal SH-SY5Y cells. We prepared cells transfected with siRNA for Nucling or nontargeting control siRNA to determine the role of Nucling in amyloid-β-induced apoptosis. The amyloid-β increased intracellular and mitochondrial ROS levels, apoptotic indices (p53, Bax/Bcl-2 ratio, caspase-3 cleavage), NF-kB activation and Nucling expression, while cell viability, mitochondrial membrane potential, and oxygen consumption rate decreased in SH-SY5Y cells. Lycopene inhibited these amyloid-β-induced alterations. However, amyloid-β did not induce apoptosis, determined by cell viability and apoptotic indices (p53, Bax/Bcl-2 ratio, caspase-3 cleavage), in the cells transfected with siRNA for Nucling. Lycopene inhibited apoptosis by reducing ROS, and by inhibiting mitochondrial dysfunction and NF-κB-target gene Nucling expression in neuronal cells. Lycopene may be beneficial for preventing oxidative stress-mediated neuronal death in patients with neurodegeneration.
Highlights
Alzheimer’s disease (AD) is a major neurodegenerative disorder, which is characterized by a progressive cognitive decline, leading to dementia
The aim of this study was to investigate whether lycopene inhibits amyloid-β-stimulated apoptotic cell death by reducing intracellular and mitochondrial Reactive oxygen species (ROS) and by suppressing mitochondrial dysfunction, NF-κB-mediated Nucling expression, and apoptotic indices in human neuronal SH-SY5Y cells
Treatment with lycopene reduced all these apoptotic responses in amyloid-β-stimulated cells. These results indicate that amyloid-β caused neuronal apoptosis, which was inhibited by lycopene
Summary
Alzheimer’s disease (AD) is a major neurodegenerative disorder, which is characterized by a progressive cognitive decline, leading to dementia. Amyloid-β oligomers tend to accumulate and are associated with neuronal degeneration. In early phase of AD, little is known about the interplay of microglia, astrocytes and neurons in response to amyloid-β. In late phase of AD, glial cells produce large amounts of inflammatory cytokines, reactive oxygen and nitrogen species, which disrupts nerve terminals activity causing memory decline and neuronal death [1]. AD is the sixth leading cause of death in Americans and the fifth leading cause of death in the United States age ≥65 years. In 2013, Alzheimer’s Association reported that 5.2 million Americans have AD. The association reported that an American develops AD every 68 s
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