Miquel-Rio Lluis, Sarriés-Serrano Unai, Pavia-Collado Rubén, Meana J Javier, Bortolozzi Analia
Institute of Biomedical Research of Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Biomedicines. 2023 Feb 13;11(2):541. doi: 10.3390/biomedicines11020541.
In patients affected by Parkinson's disease (PD), up to 50% of them experience cognitive changes, and psychiatric disturbances, such as anxiety and depression, often precede the onset of motor symptoms and have a negative impact on their quality of life. Pathologically, PD is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of intracellular inclusions, called Lewy bodies and Lewy neurites, composed mostly of α-synuclein (α-Syn). Much of PD research has focused on the role of α-Syn aggregates in the degeneration of SNc DA neurons due to the impact of striatal DA deficits on classical motor phenotypes. However, abundant Lewy pathology is also found in other brain regions including the midbrain raphe nuclei, which may contribute to non-motor symptoms. Indeed, dysfunction of the serotonergic (5-HT) system, which regulates mood and emotional pathways, occurs during the premotor phase of PD. However, little is known about the functional consequences of α-Syn inclusions in this neuronal population other than DA neurons. Here, we provide an overview of the current knowledge of α-Syn and its role in regulating the 5-HT function in health and disease. Understanding the relative contributions to α-Syn-linked alterations in the 5-HT system may provide a basis for identifying PD patients at risk for developing depression and could lead to a more targeted therapeutic approach.
在帕金森病（PD）患者中，高达50%的人会出现认知变化，而诸如焦虑和抑郁等精神障碍往往在运动症状出现之前就已出现，并对他们的生活质量产生负面影响。在病理上，PD的特征是黑质致密部（SNc）中多巴胺（DA）神经元的丧失以及细胞内包含物的存在，这些包含物称为路易小体和路易神经突，主要由α-突触核蛋白（α-Syn）组成。由于纹状体DA缺乏对经典运动表型的影响，许多PD研究都集中在α-Syn聚集体在SNc DA神经元变性中的作用。然而，在包括中脑缝核在内的其他脑区也发现了大量路易病理，这可能导致非运动症状。事实上，调节情绪和情感通路的血清素能（5-HT）系统功能障碍发生在PD的运动前期。然而，除了DA神经元外，关于α-Syn包含物在这个神经元群体中的功能后果知之甚少。在这里，我们概述了目前关于α-Syn及其在健康和疾病中调节5-HT功能作用的知识。了解α-Syn相关的5-HT系统改变的相对贡献可能为识别有患抑郁症风险的PD患者提供基础，并可能导致更有针对性的治疗方法。
