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ω-3多不饱和脂肪酸对帕金森病的潜在治疗作用

Potential treatment of Parkinson's disease with omega-3 polyunsaturated fatty acids.

作者信息

Li Peng, Song Cai

机构信息

Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, People's Republic of China.

Stem Cell Research and Cellular Therapy Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People's Republic of China.

出版信息

Nutr Neurosci. 2022 Jan;25(1):180-191. doi: 10.1080/1028415X.2020.1735143. Epub 2020 Mar 3.

Abstract

Parkinson's disease (PD) is characterized by dysfunction of the nigrostriatal system, loss of dopamine neurons and intracellular aggregation of α-synuclein. Recently, both clinical and experimental studies have reported that neuroinflammation and oxidative stress markedly contribute to the etiology of PD. Current clinical pharmacotherapies only temporarily relieve the symptoms of PD, accompanied by many side effects. Hence, searching for natural anti-inflammatory, anti-oxidative and neuroprotective agents has received great attention. Polyunsaturated fatty acids (PUFAs), especially omega (n)-3, are essential lipid nutrients in the human diet and important components of cell membranes. Together by competing with the production of n-6 PUFAs, the precursors of inflammatory mediators, n-3 PUFAs can inhibit microglial activity and neuroinflammation, protect astrocyte function to produce neurotrophins, thereby normalizing neurotransmission and improving neurodegeneration. Thus, with regard to the hypotheses of PD, our and other's recent studies have demonstrated that n-3 PUFAs may improve PD by inhibiting proinflammatory cytokine release, promoting neurotrophic factor expression, recovering mitochondrial function and membrane fluidity, decreasing the levels of oxidant production, maintaining α-synuclein proteostasis, calcium homeostasis, axonal transport, and reducing endoplasmic reticulum stress. This review mainly introduces and analyzes the effect of n-3 PUFA treatments on PD-related behavioral and neuropathological abnormalities in clinical patients and different cellular and animal models of PD. Finally, the limitations and future work in n-3 PUFAs anti-PD area are discussed.

摘要

帕金森病(PD)的特征是黑质纹状体系统功能障碍、多巴胺能神经元丧失以及α-突触核蛋白在细胞内聚集。最近,临床和实验研究均报道神经炎症和氧化应激在帕金森病的病因中起显著作用。目前的临床药物治疗仅能暂时缓解帕金森病症状,且伴有许多副作用。因此,寻找天然的抗炎、抗氧化和神经保护剂受到了广泛关注。多不饱和脂肪酸(PUFAs),尤其是ω(n)-3脂肪酸,是人类饮食中必需的脂质营养素,也是细胞膜的重要组成部分。通过与炎症介质前体n-6多不饱和脂肪酸的生成相互竞争,n-3多不饱和脂肪酸可以抑制小胶质细胞活性和神经炎症,保护星形胶质细胞功能以产生神经营养因子,从而使神经传递正常化并改善神经退行性变。因此,关于帕金森病的假说,我们和其他团队最近的研究表明,n-3多不饱和脂肪酸可能通过抑制促炎细胞因子释放、促进神经营养因子表达、恢复线粒体功能和膜流动性、降低氧化剂生成水平、维持α-突触核蛋白蛋白稳态、钙稳态、轴突运输以及减轻内质网应激来改善帕金森病。本综述主要介绍并分析了n-3多不饱和脂肪酸治疗对临床患者以及不同帕金森病细胞和动物模型中与帕金森病相关的行为和神经病理异常的影响。最后,讨论了n-3多不饱和脂肪酸在抗帕金森病领域的局限性和未来研究方向。

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