Neuregulin-1 Exerts Protective Effects Against Neurotoxicities Induced by C-Terminal Fragments of APP via ErbB4 Receptor
| Autor: | Ha Nul Yu, Soo Joo Lee, Tai Kyoung Baik, Junghwa Ryu, Ran Sook Woo, Harim Cho, Hye Sun Kim |
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| Rok vydání: | 2012 |
| Předmět: |
Receptor
ErbB-4 Amyloid Amyloid beta Neuregulin-1 Neuroprotection Amyloid beta-Protein Precursor Alzheimer Disease mental disorders medicine Amyloid precursor protein Humans Neuregulin 1 Receptor ERBB4 Membrane Potential Mitochondrial Neurons Pharmacology Amyloid beta-Peptides Cell Death biology Superoxide Dismutase Chemistry lcsh:RM1-950 Neurotoxicity Brain medicine.disease Peptide Fragments Up-Regulation Cell biology ErbB Receptors Neuroprotective Agents lcsh:Therapeutics. Pharmacology Proto-Oncogene Proteins c-bcl-2 biology.protein Molecular Medicine Neurotoxicity Syndromes Apoptosis Regulatory Proteins Reactive Oxygen Species |
| Zdroj: | Journal of Pharmacological Sciences, Vol 119, Iss 1, Pp 73-81 (2012) |
| ISSN: | 1347-8648 1347-8613 |
| DOI: | 10.1254/jphs.12057fp |
| Popis: | 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. Keywords:: Alzheimer’s disease, neuregulin-1, ErbB4, C-terminal fragment of amyloid precursor protein |
| Databáze: | OpenAIRE |
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