Butkovich Laura M, Houser Madelyn C, Tansey Malú G
Tansey Laboratory, Department of Physiology, School of Medicine, Emory University, Atlanta, GA, United States.
Front Neurosci. 2018 Sep 11;12:626. doi: 10.3389/fnins.2018.00626. eCollection 2018.
α-synuclein (α-syn) pathology and loss of noradrenergic neurons in the locus coeruleus (LC) are among the most ubiquitous features of Parkinson's disease (PD). While noradrenergic dysfunction is associated with non-motor symptoms of PD, preclinical research suggests that the loss of LC norepinephrine (NE), and subsequently its immune modulatory and neuroprotective actions, may exacerbate or even accelerate disease progression. In this review, we discuss the mechanisms by which α-syn pathology and loss of central NE may directly impact brain health by interrupting neurotrophic factor signaling, exacerbating neuroinflammation, and altering regulation of innate and adaptive immune cells.
α-突触核蛋白（α-syn）病理改变和蓝斑（LC）中去甲肾上腺素能神经元的丧失是帕金森病（PD）最普遍的特征之一。虽然去甲肾上腺素能功能障碍与PD的非运动症状有关，但临床前研究表明，LC中去甲肾上腺素（NE）的丧失以及随后其免疫调节和神经保护作用的丧失，可能会加剧甚至加速疾病进展。在这篇综述中，我们讨论了α-syn病理改变和中枢NE丧失可能通过中断神经营养因子信号传导、加剧神经炎症以及改变固有免疫细胞和适应性免疫细胞的调节而直接影响脑健康的机制。
