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Neuregulin-1 exerts protective effects against neurotoxicities induced by C-terminal fragments of APP via ErbB4 receptor
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نویسنده
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ryu j. ,yu h.-n. ,cho h. ,kim h.-s. ,baik t.-k. ,lee s.-j. ,woo r.-s.
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منبع
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journal of pharmacological sciences - 2012 - دوره : 119 - شماره : 1 - صفحه:73 -81
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چکیده
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Neuregulin-1 (nrg1) plays important roles in the development and plasticity of the brain,and it is also reported to have potent neuroprotective properties. we previously reported that nrg1 has neuroprotective actions against swedish amyloid precursor protein-induced neurotoxicity. in addition to the amyloid beta peptide,other metabolites of amyloid precursor protein (app) such as the c-terminal fragments of app (app-cts) have been reported to possess cytotoxic effects in neuronal cells. in this study,we investigated whether nrg1 exerts neuroprotective effects against app-cts and attempted to determine its neuroprotective mechanisms. nrg1 attenuated the neurotoxicities induced by the expression of app-cts in neuronal cells. nrg1 also reduced the accumulation of reactive oxygen species and attenuated mitochondrial membrane potential loss induced by app-cts. in addition,nrg1 upregulated the expression of the antiapoptotic protein bcl-2. this effect was blocked by the inhibition of erbb4,a key nrg1 receptor. taken together,these results demonstrate the neuroprotective potential of nrg1 in alzheimer's disease.
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کلیدواژه
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Alzheimer's disease; C-terminal fragment of amyloid precursor protein; ErbB4; Neuregulin-1
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آدرس
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department of pharmacology and biomedical sciences,college of medicine,seoul national university,seoul 110-799, South Korea, department of anatomy and neuroscience,college of medicine,eulji university,daejeon 301-746, South Korea, department of pharmacology and biomedical sciences,college of medicine,seoul national university,seoul 110-799, South Korea, department of pharmacology and biomedical sciences,college of medicine,seoul national university,seoul 110-799,south korea,seoul national university bundang hospital,seoul national university,college of medicine,bundang-gu,sungnam 463-707, South Korea, department of anatomy and neuroscience,college of medicine,eulji university,daejeon 301-746, South Korea, department of neurology,eulji university hospital,daejeon 302-799, South Korea, department of anatomy and neuroscience,college of medicine,eulji university,daejeon 301-746, South Korea
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Authors
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