Publication: Neuroprotection of SAK3 on scopolamine-induced cholinergic dysfunction in human neuroblastoma SH-SY5Y cells
Issued Date
2020-01-01
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ISSN
15730778
09209069
09209069
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2-s2.0-85077871097
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Mahidol University
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SCOPUS
Bibliographic Citation
Cytotechnology. (2020)
Suggested Citation
Nopparat Suthprasertporn, Nopparada Mingchinda, Kohji Fukunaga, Wipawan Thangnipon Neuroprotection of SAK3 on scopolamine-induced cholinergic dysfunction in human neuroblastoma SH-SY5Y cells. Cytotechnology. (2020). doi:10.1007/s10616-019-00366-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/49545
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Title
Neuroprotection of SAK3 on scopolamine-induced cholinergic dysfunction in human neuroblastoma SH-SY5Y cells
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Abstract
© 2020, Springer Nature B.V. Alzheimer’s disease (AD) is the most common type of senile dementia. A number of factors have been proposed regarding pathology of AD, such as presence of β-amyloid, and cholinergic and oxidative stress. SAK3 (ethyl 8′-methyl-2′,5-dioxo-2-piperidin-1-ylspiro[cyclopentene-3,3′-imidazo[1,2-a]pyridine]-1-carboxylate) reduces β-amyloid deposition and improves cognitive functions in amyloid precursor protein knock-in mice. Scopolamine is used to induce in cell lines a cholinergic deficit that mimics AD. In order to evaluate the possible neuroprotective properties of SAK3, human neuroblastoma SH-SY5Y cells were pretreated with the compound (25–100 nM) and further incubated in the presence of scopolamine (2 mM). SAK3 inhibited scopolamine-induced cellular apoptosis (morphologically and by determination of pro- and anti-apoptotic factor levels), increase in ROS levels, decrease in choline acetyltransferase level, phosphorylation of NF-κB, activation of Akt, JNK and p38 intracellular signaling pathways, and elevation of proinflammatory cytokines IL-1β and IL-6, but not enhanced level of β-site amyloid precursor protein cleaving enzyme 1 (BACE1). These results indicate SAK3 possessed protective properties against cholinergic deficit associated with anti-oxidant, anti-apoptotic and anti-inflammatory activities, suggesting that SAK3 might be a potential agent in the development of AD drug therapeutics.