α-Arbutin Protects Against Parkinson’s Disease-Associated Mitochondrial Dysfunction In Vitro and In Vivo
Autor: | Tong Zhou, Naidi Yang, Lin Li, Qiong Wu, Kah-Leong Lim, Wei Huang, Yaqi Ding, Jiajia Xu, Qi Wang, Chenqi Xin, Ma Bo, Chengwu Zhang, Xiaomei Lu, Deqin Kong, Hang Zhang |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Parkinson's disease Drug Evaluation Preclinical Apoptosis Mitochondrion Pharmacology medicine.disease_cause Antioxidants Parkin Neuroblastoma chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Drosophila Proteins Medicine Membrane Potential Mitochondrial Arbutin Parkinson Disease Mitochondria Drosophila melanogaster Neuroprotective Agents Neurology Molecular Medicine Ericaceae Female Oxidation-Reduction Ubiquitin-Protein Ligases Substantia nigra Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience Parkinsonian Disorders Cell Line Tumor Rotenone Autophagy Animals Humans Plant Extracts business.industry Adenylate Kinase medicine.disease Oxidative Stress 030104 developmental biology chemistry business 030217 neurology & neurosurgery Oxidative stress Phytotherapy |
Zdroj: | NeuroMolecular Medicine. 22:56-67 |
ISSN: | 1559-1174 1535-1084 |
Popis: | Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by the progressive loss of dopaminergic neurons in substantia nigra. The underlying mechanisms of PD pathogenesis have not been fully illustrated and currently PD remains incurable. Accumulating evidences suggest that mitochondrial dysfunction plays pivotal role in the dopaminergic neuronal death. Therefore, discovery of novel and safe agent for rescuing mitochondrial dysfunction would benefit PD treatment. Here we demonstrated for the first time that α-Arbutin (Arb), a natural polyphenol extracted from Ericaceae species, displayed significant protective effect on the rotenone (Rot)-induced mitochondrial dysfunction and apoptosis of human neuroblastoma cell (SH-SY5Y). We further found that the neuroprotective effect of Arb was associated with ameliorating oxidative stress, stabilizing of mitochondrial membrane potential, and enhancing adenosine triphosphate production. To investigate the underlying mechanism, we checked the AMP-activated protein kinase and autophagy pathway and we found that both were involved in the neuroprotection of Arb. Moreover, we explored the protective effect of Arb in drosophila PD model and found that Arb rescued parkin deficiency-induced motor function disability and mitochondrial abnormality of drosophila. Taken together, our study demonstrated that Arb got excellent neuroprotective effect on PD models both in vitro and in vivo and Arb might serve as a potent therapeutic agent for the treatment of PD. |
Databáze: | OpenAIRE |
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