Longhena Francesca, Faustini Gaia, Missale Cristina, Pizzi Marina, Spano PierFranco, Bellucci Arianna
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; IRCCS Fondazione Ospedale San Camillo (NHS-Italy), Venice Lido, Italy.
Neural Plast. 2017;2017:5012129. doi: 10.1155/2017/5012129. Epub 2017 Jan 3.
Synaptopathies are diseases with synapse defects as shared pathogenic features, encompassing neurodegenerative disorders such as Parkinson's disease (PD). In sporadic PD, the most common age-related neurodegenerative movement disorder, nigrostriatal dopaminergic deficits are responsible for the onset of motor symptoms that have been related to -synuclein deposition at synaptic sites. Indeed, -synuclein accumulation can impair synaptic dopamine release and induces the death of nigrostriatal neurons. While in physiological conditions the protein can interact with and modulate synaptic vesicle proteins and membranes, numerous experimental evidences have confirmed that its pathological aggregation can compromise correct neuronal functioning. In addition, recent findings indicate that -synuclein pathology spreads into the brain and can affect the peripheral autonomic and somatic nervous system. Indeed, monomeric, oligomeric, and fibrillary -synuclein can move from cell to cell and can trigger the aggregation of the endogenous protein in recipient neurons. This novel "prion-like" behavior could further contribute to synaptic failure in PD and other synucleinopathies. This review describes the major findings supporting the occurrence of -synuclein pathology propagation in PD and discusses how this phenomenon could induce or contribute to synaptic injury and degeneration.
突触病是以突触缺陷为共同致病特征的疾病，包括帕金森病（PD）等神经退行性疾病。在散发性PD中，这是最常见的与年龄相关的神经退行性运动障碍，黑质纹状体多巴胺能缺陷导致运动症状的出现，这些症状与突触部位的α-突触核蛋白沉积有关。事实上，α-突触核蛋白的积累会损害突触多巴胺释放，并诱导黑质纹状体神经元死亡。在生理条件下，该蛋白可与突触囊泡蛋白和膜相互作用并进行调节，但大量实验证据证实其病理聚集会损害神经元的正常功能。此外，最近的研究结果表明，α-突触核蛋白病理会扩散到大脑，并可影响外周自主神经系统和躯体神经系统。实际上，单体、寡聚体和纤维状的α-突触核蛋白可以在细胞间移动，并可触发受体神经元中内源性蛋白的聚集。这种新的“朊病毒样”行为可能会进一步导致PD和其他突触核蛋白病中的突触功能障碍。这篇综述描述了支持α-突触核蛋白病理在PD中传播的主要研究结果，并讨论了这种现象如何诱导或导致突触损伤和退化。
