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 cell system, cultured under decreasing levels of BDNF and aggregated Aβ, 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.
journal_name
Biol Pharm Bulljournal_title
Biological & pharmaceutical bulletinauthors
Tagai N,Tanaka A,Sato A,Uchiumi F,Tanuma SIdoi
10.1248/bpb.b20-00082subject
Has Abstractpub_date
2020-01-01 00:00:00pages
1073-1080issue
7eissn
0918-6158issn
1347-5215journal_volume
43pub_type
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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journal_title:Biological & pharmaceutical bulletin
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