Passion fruit seed extract protects beta-amyloid-induced neuronal cell death in a differentiated human neuroblastoma SH-SY5Y cell model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with accompanying perceptive disorder. We previously reported that decreasing levels of brain-derived neurotrophic factor (BDNF) promoted beta-amyloid (Aß)-induced neuronal cell death in neuron-like differentiated SH-SY5Y (ndSH-SY5Y) human neuroblastoma cells in an AD mimic cell model. We investigated the neuroprotective effects of passion fruit seed extract (PFSE) and one of the main stilbene compounds, piceatannol, in an AD cell model using ndSH-SY5Y cells. Both PFSE and piceatannol were found to protect Aß-induced neurite fragmentation in the cell model (protection efficacy; 34% in PFSE and 36% in piceatannol). In addition, both PFSE and piceatannol suppress Aß-induced neuronal cell death in the cell model (inhibitory effect; 27% in PFSE and 32% in piceatannol). Our study is the first to report that piceatannol-rich PFSE can repress Aß-induced neuronal cell death by protecting against neurite fragmentation in the AD human cell model. These findings suggest that piceatannol-rich PFSE can be considered a potentially neuroprotective functional food for both prevention and treatment of AD.

Low Levels of Brain-Derived Neurotrophic Factor Trigger Self-aggregated Amyloid ß-Induced Neuronal Cell Death in an Alzheimer's Cell Model.

Alzheimer's disease (AD) is pathologically characterized by accumulation of amyloid ß (Aß) and hyperphosphorylated tau, and thereby induction of neuronal cell death. The Aß-induced neuronal cell death has been shown to occur by several modes, such as apoptosis, necrosis, and necroptosis. Interestingly, in AD patients, the brain and serum levels of brain-derived neurotrophic factor (BDNF) have been reported to be significantly decreased. However, the relationship between Aß and BDNF in the onset of AD remains to be fully understood. Here, we used neuron-like differentiated human neuroblastoma SH-SY5Y (ndSH-SY5Y) cells to study the neurotoxicity of self-aggregated Aß1-42 peptide under different concentrations of BDNF in the culture medium. Importantly, decreasing levels of BDNF caused a considerable suppression in the extension of neurite length. Furthermore, only under low levels of BDNF, the aggregated Aß was revealed to induce neurite fragmentation and neuronal cell death in ndSH-SY5Y cells. Notably, the aggregated Aß and low levels of BDNF-induced neuronal cell death was characterized at least as caspase-6 dependent cell death and necroptosis. These results indicate that our ndSH-SY5Y cell system, cultured under decreasing levels of BDNF and aggregated Aß, has the potential to be applied in the analysis of the molecular mechanisms of the progressive neurodegenerative processes of AD and the discovery of neuroprotective drug candidates.