• Xiaomei Liang, Yutong Wen, Cuilian Feng, Lan Xu, Ying Xian, Haiting Xie, Jianou Huang, Yihong Huang, Xiaodong Zhao, and Xiaoya Gao.
• Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, China; Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province 510080, China.
• Neuroscience. 2024 Dec 6; 562: 435343-53.

AbstractThe study aimed to validate the protective effect of neuroglobin (Ngb) in a cell model of Parkinson's disease (PD) and explore its therapeutic potential. Lentivirus-Ngb (LvNgb) and siRNA-Ngb (siNgb) were used to achieve Ngb overexpression and knockdown, respectively, in a sporadic PD cell model. Apoptosis was evaluated by flow cytometry-based Annexin V/propidium iodide assays. Activation of the pro-apoptotic factor, Caspase-9, was detected by immunoblotting, and Complex I activities were detected by using enzyme-linked immunosorbent assay (ELISA). Mitochondrial dysfunction was examined by measuring the mitochondrial membrane potential (MMP), NAD+/NADH ratios, and reactive oxygen species (ROS) levels. Additionally, coimmunoprecipitation (Co-IP) assays were conducted in mouse neuroblastoma cell line 9D (MN9D) cells to determine the interactions of Ngb with the Complex I subunit NDUFA10. The results showed that Ngb overexpression reduced the percentages of apoptotic cells, total caspase-9 levels and restored Complex I activities in the PD cell model. Conversely, knockdown of Ngb resulted in an increase in apoptotic cells, higher total caspase-9 levels, and decreased Complex I activities. Furthermore, Ngb overexpression restored MMP and NAD+/NADH ratios and alleviated ROS-mediated oxidative stress in MN9D cells. Finally, Co-IP confirmed the interaction between Ngb and NDUFA10 in MN9D cells. In conclusion, Ngb protects MN9D cells against apoptosis by interacting with Complex I subunit NDUFA10, rescuing its activity and inhibiting the mitochondrial pathway of apoptosis in the MPP+-mediated PD model.Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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