Protective Role of AMPK against PINK1B9 Flies' Neurodegeneration with Improved Mitochondrial Function

Guoliang Xiang; Xueyi Wen; Wenjing Wang; Tianchan Peng; Jiazhen Wang; Qinghua Li; Junfang Teng; Ying Cui

doi:10.1155/2023/4422484

Protective Role of AMPK against PINK1^B9 Flies' Neurodegeneration with Improved Mitochondrial Function

Parkinsons Dis. 2023 Oct 12:2023:4422484. doi: 10.1155/2023/4422484. eCollection 2023.

Authors

Guoliang Xiang¹, Xueyi Wen^{2

3}, Wenjing Wang², Tianchan Peng², Jiazhen Wang², Qinghua Li^{2

4}, Junfang Teng^{1

5}, Ying Cui^{1

2

4

5}

Affiliations

¹ Department of Neurology Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
² Department of Neurology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi 541004, China.
³ Department of Neurology and Stroke Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
⁴ Department of Neurology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
⁵ Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

Abstract

Adenosine 5'-monophosphate-activated protein kinase (AMPK)'s effect in PTEN-induced kinase 1 (PINK1) mutant Parkinson's disease (PD) transgenic flies and the related mechanism is seldom studied. The classic MHC-Gal4/UAS PD transgenic flies was utilized to generate the disease characteristics specifically expressed in flies' muscles, and Western blot (WB) was used to measure the expression of the activated form of AMPK to investigate whether activated AMPK alters in PINK1^B9 PD flies. MHC-Gal4 was used to drive AMPK overexpression in PINK1^B9 flies to demonstrate the crucial role of AMPK in PD pathogenesis. The abnormal wing posture and climbing ability of PINK1^B9 PD transgenic flies were recorded. Mitochondrial morphology via transmission electron microscopy (TEM) and ATP and NADH: ubiquinone oxidoreductase core subunit S3 (NDUFS3) protein levels were tested to evaluate the alteration of the mitochondrial function in PINK1^B9 PD flies. Phosphorylated AMPKα dropped significantly in PINK1^B9 flies compared to controls, and AMPK overexpression rescued PINK^B9 flies' abnormal wing posture rate. The elevated dopaminergic neuron number in PPL1 via immunofluorescent staining was observed. Mitochondrial dysfunction in PINK1^B9 flies has been ameliorated with increased ATP level, restored mitochondrial morphology in muscle, and increased NDUFS3 protein expression. Conclusively, AMPK overexpression could partially rescue the PD flies via improving PINK1^B9 flies' mitochondrial function.