Neuroglobin Attenuates Beta Amyloid-Induced Apoptosis Through Inhibiting Caspases Activity by Activating PI3K/Akt Signaling Pathway.
Excessive accumulation and deposition of amyloid-beta (Aβ) has been considered as a pivotal event in the pathogenesis of Alzheimer's disease (AD). Neuronal apoptosis is one of the characteristics of AD, which is a possible mechanism underlying Aβ-induced neuronal neurotoxicity. Neuroglobin (Ngb) is a newly discovered vertebrate heme protein that exhibits neuroprotective functions against cell death associated with hypoxic and amyloid insult. However, until now, the exact mechanism of neuroglobin's protective action has not been determined. To investigate the potential neuroprotective roles and mechanisms of Ngb, transgenic AD mice (APPswe/PSEN1dE9) and SH-SY5Y cells transfected with pAPPswe were enrolled into the study. In vivo, overexpression of Ngb via intracerebroventricular injection with pNgb attenuated memory, cognitive impairment, and plaque generations. In pAPPswe transfected SH-SY5Y cells, Ngb not only decreased the generation of Aβ42, but also attenuated mitochondrial dysfunction and apoptosis through suppressing the activation of caspase-3, caspase-9 by Akt activating phosphorylation, which were restrained by phosphatidylinositol 3-kinase inhibitor (LY294002). Our data indicate the anti-apoptotic property of Ngb may play a neuroprotective role against AD.
Department of Pathology, Chongqing Medical University, Chongqing, China.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.
Yu
Y
Li
Department of Otolaryngology, Guizhou Provincial People's Hospital, Guiyang, China.
Yu-bing
YB
Dai
Department of Pathology, Chongqing Medical University, Chongqing, China.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.
Jie-yun
JY
Sun
Department of Pathology, Chongqing Medical University, Chongqing, China.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.
Yue
Y
Xiang
Department of Pathology, Chongqing Medical University, Chongqing, China.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.
Jun
J
Yang
Department of Pathology, Chongqing Medical University, Chongqing, China.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China.
Song-yang
SY
Dai
Department of Pathology, Chongqing Medical University, Chongqing, China. zhangxiong_0@aliyun.com.|Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China. zhangxiong_0@aliyun.com.|Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China. zhangxiong_0@aliyun.com.
Xiong
X
Zhang
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015290:Second Messenger Systems
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9
Alzheimer’s disease; Beta amyloid; Caspases; Neuroglobin; PI3K/Akt pathway