Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Full Paper
Neuregulin-1 Exerts Protective Effects Against Neurotoxicities Induced by C-Terminal Fragments of APP via ErbB4 Receptor
Junghwa RyuHa-Nul YuHarim ChoHye-Sun KimTai-Kyoung BaikSoo-Joo LeeRan-Sook Woo
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2012 Volume 119 Issue 1 Pages 73-81

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Abstract

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 anti-apoptotic 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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© 2012 The Japanese Pharmacological Society
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