Guan Lihua, Lin Liling, Ma Chaochao, Qiu Ling
Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, PR China.
Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100730, PR China.
Ther Adv Neurol Disord. 2025 Jun 5;18:17562864251339895. doi: 10.1177/17562864251339895. eCollection 2025.
Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by progressive worsening of motor symptoms. The primary pathological hallmark of PD is the degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are primarily composed of α-synuclein (α-syn) aggregates. Both α-syn and various neurotransmitters, including catecholamines (catechols), play crucial roles in the pathogenesis of PD, although the precise pathogenic mechanisms remain incompletely understood. The crosstalk between neurotransmitters and α-syn is intricate and multifaceted. Pathological α-syn disrupted neurotransmitters' homeostasis by impairing release and reuptake of neurotransmitters, with specific modulation of catecholaminergic and glutamatergic systems. Conversely, neurotransmitters, especially catechols, covalently modify α-syn. Such modifications significantly influence α-syn aggregation dynamics and alter its neurotoxic properties. However, determining whether these interactions induce synergistic toxicity or confer neuroprotection remains controversial. Emerging evidence suggests other neurotransmitters like serotonin and γ-aminobutyric acid may also modulate α-syn aggregation and PD progression, though their roles require further investigation. Understanding these interactions is crucial for developing novel diagnostic and multi-target therapeutic strategies.
帕金森病（PD）是第二常见的神经退行性疾病，其特征是运动症状逐渐恶化。PD的主要病理标志是黑质中多巴胺能神经元的退化以及路易小体的存在，路易小体主要由α-突触核蛋白（α-syn）聚集体组成。尽管确切的致病机制仍未完全了解，但α-syn和包括儿茶酚胺（儿茶酚）在内的各种神经递质在PD的发病机制中都起着关键作用。神经递质与α-syn之间的相互作用错综复杂且具有多面性。病理性α-syn通过损害神经递质的释放和再摄取来破坏神经递质的稳态，对儿茶酚胺能和谷氨酸能系统有特定调节作用。相反，神经递质，尤其是儿茶酚，可对α-syn进行共价修饰。这种修饰会显著影响α-syn的聚集动力学并改变其神经毒性特性。然而，确定这些相互作用是诱导协同毒性还是赋予神经保护作用仍存在争议。新出现的证据表明，血清素和γ-氨基丁酸等其他神经递质也可能调节α-syn聚集和PD进展，不过它们的作用还需要进一步研究。了解这些相互作用对于开发新的诊断和多靶点治疗策略至关重要。
