Neuregulin-1 exerts protective effects against neurotoxicities induced by C-terminal fragments of APP via ErbB4 receptor.
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.
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Republic of Korea.
Junghwa
J
Ryu
Ha-Nul
HN
Yu
Harim
H
Cho
Hye-Sun
HS
Kim
Tai-Kyoung
TK
Baik
Soo-Joo
SJ
Lee
Ran-Sook
RS
Woo
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D020890:Neuregulin-1 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D066247:Receptor, ErbB-4; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; C094131:NRG1 protein, human; D020890:Neuregulin-1; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4