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

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 PINK1B9 PD flies. MHC-Gal4 was used to drive AMPK overexpression in PINK1B9 flies to demonstrate the crucial role of AMPK in PD pathogenesis. The abnormal wing posture and climbing ability of PINK1B9 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 PINK1B9 PD flies. Phosphorylated AMPKα dropped significantly in PINK1B9 flies compared to controls, and AMPK overexpression rescued PINKB9 flies' abnormal wing posture rate. The elevated dopaminergic neuron number in PPL1 via immunofluorescent staining was observed. Mitochondrial dysfunction in PINK1B9 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 PINK1B9 flies' mitochondrial function.

• Authors: Guoliang Xiang, Xueyi Wen, Wenjing Wang, Tianchan Peng, Jiazhen Wang, Qinghua Li, Junfang Teng, Ying Cui
• Journal: Parkinson's disease (Parkinsons Dis) Vol. 2023 Pg. 4422484 ( 2023) ISSN: 2090-8083 [Print] United States
• PMID: 37868355 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Guoliang Xiang et al.