Parkinson’s disease (PD) is the second most common neurodegenerative disease. Currently, PD has no treatment. The neuronal protein α-synuclein (αS) plays an important role in PD. However, the molecular mechanisms governing its physiological and pathological roles are not fully understood. It is becoming widely acknowledged that the biological roles of αS involve interactions with biological membranes. In these biological processes there is a fine-tuned interplay between lipids affecting the properties of αS and αS affecting lipid metabolism, αS binding to membranes, and membrane damage. In this review, the intricate interactions between αS and membranes will be reviewed and a discussion of the relationship between αS and neuronal membrane structural plasticity in health and disease will be made. It is proposed that in healthy neurons the conformational flexibilities of αS and the neuronal membranes are coupled to assist the physiological roles of αS. However, in circumstances where their conformational flexibilities are decreased or uncoupled, there is a shift toward cell toxicity. Strategies to modulate toxic αS-membrane interactions are potential approaches for the development of new therapies for PD. Future work using specific αS molecular species as well as membranes with specific physicochemical properties should widen our understanding of the intricate biological roles of αS which, in turn, would propel the development of new strategies for the treatment of PD.

帕金森病 (PD) 是第二常见的神经退行性疾病。目前，PD没有治疗方法。神经元蛋白 α-突触核蛋白 (αS) 在 PD 中起重要作用。然而，控制其生理和病理作用的分子机制尚不完全清楚。人们普遍承认αS的生物学作用涉及与生物膜的相互作用。在这些生物过程中，影响 αS 特性的脂质和影响脂质代谢的 αS、αS 与膜的结合和膜损伤之间存在微调的相互作用。在这篇综述中，将回顾 αS 与膜之间复杂的相互作用，并讨论 αS 与健康和疾病中神经元膜结构可塑性之间的关系。有人提出，在健康神经元中，αS 的构象灵活性和神经元膜耦合以辅助 αS 的生理作用。然而，在它们的构象灵活性降低或解偶联的情况下，细胞毒性会发生转变。调节毒性αS-膜相互作用的策略是开发PD新疗法的潜在方法。使用特定 αS 分子种类以及具有特定理化特性的膜的未来工作应该会拓宽我们对 αS 复杂生物学作用的理解，这反过来将推动治疗 PD 的新策略的发展。在它们的构象灵活性降低或解偶联的情况下，会转向细胞毒性。调节毒性αS-膜相互作用的策略是开发PD新疗法的潜在方法。使用特定 αS 分子种类以及具有特定理化特性的膜的未来工作应该会拓宽我们对 αS 复杂生物学作用的理解，这反过来将推动治疗 PD 的新策略的发展。在它们的构象灵活性降低或解偶联的情况下，会转向细胞毒性。调节毒性αS-膜相互作用的策略是开发PD新疗法的潜在方法。使用特定 αS 分子种类以及具有特定理化特性的膜的未来工作应该会拓宽我们对 αS 复杂生物学作用的理解，这反过来将推动治疗 PD 的新策略的发展。