多不饱和脂肪酸在帕金森病中的作用机制 研究进展
Research Progress on the Mechanisms of Polyunsaturated Fatty Acids in Parkinson’s Disease
DOI: 10.12677/acm.2026.1641387, PDF,   
作者: 杨 丽, 朱 丹*：重庆医科大学附属第一医院神经内科，重庆；杨琰琤：中国人民解放军陆军第九五八医院预防保健科，重庆
关键词: 帕金森病；多不饱和脂肪酸；ω-3脂肪酸；ω-6脂肪酸；Parkinson’s Disease； Polyunsaturated Fatty Acids； Omega-3 Fatty Acids； Omega-6 Fatty Acids
摘要: 帕金森病(PD)传统上被视为以α-突触核蛋白(α-syn)错误折叠为核心的蛋白病，但越来越多证据表明脂质代谢异常可能在疾病发生中发挥关键作用。多不饱和脂肪酸(PUFAs)作为神经膜的重要组成成分，既可通过调节膜微环境促进α-syn构象改变和脂质过氧化放大环路，又可通过抗炎、抗氧化及神经营养支持机制发挥神经保护作用。脂质过氧化产物如4-羟基壬烯醛(4-HNE)可共价修饰α-syn并增强其毒性寡聚化，而ω-3脂肪酸在特定条件下则可激活NRF2及神经营养通路。然而，DHA在部分模型中亦促进α-syn寡聚化，提示脂肪酸在PD中具有情境依赖性和“双刃剑效应”。本文系统整合脂肪酸-α-syn相互作用、脂质过氧化放大机制及线粒体–炎症交互环路的最新研究进展，提出脂质代谢异常可能构成PD病理放大轴，并探讨其作为干预靶点的潜在价值。
Abstract: Emerging evidence suggests that Parkinson’s disease (PD) may not solely represent a proteinopathy but also involve lipid metabolic dysregulation. Polyunsaturated fatty acids (PUFAs), as essential membrane components, exert dual effects in PD pathogenesis. On one hand, their high susceptibility to peroxidation promotes lipid-derived reactive aldehydes such as 4-hydroxynonenal (4-HNE), which covalently modify α-synuclein (α-syn) and enhance toxic oligomerization, thereby contributing to mitochondrial dysfunction and oxidative stress amplification. On the other hand, omega-3 fatty acids, including DHA and EPA, may activate NRF2 signaling, upregulate neurotrophic factors, and attenuate neuroinflammation. The context-dependent interplay between oxidative environment, fatty acid composition, and α-syn aggregation suggests a bidirectional regulatory mechanism. This review proposes a lipid peroxidation-α-syn-mitochondrial dysfunction amplification axis and discusses its therapeutic implications in PD.
文章引用：杨丽, 杨琰琤, 朱丹. 多不饱和脂肪酸在帕金森病中的作用机制 研究进展[J]. 临床医学进展, 2026, 16(4): 1524-1531. https://doi.org/10.12677/acm.2026.1641387

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