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

Low Levels of Brain-Derived Neurotrophic Factor Trigger Self-aggregated Amyloid β-Induced Neuronal Cell Death in an Alzheimer's Cell Model. Biol Pharm Bull. 2020;43(7):1073-1080 Authors: Tagai N, Tanaka A, Sato A, Uchiumi F, Tanuma SI Abstract Alzheimer's disease (AD) is pathologically characterized by accumulation of amyloid β (Aβ) and hyperphosphorylated tau, and thereby induction of neuronal cell death. The Aβ-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 Aβ 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 Aβ1-42 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 Aβ was revealed to induce neurite fragmentation and neuronal cell death in ndSH-SY5Y cells. Notably, the aggregated Aβ 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...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research