T cells, α-synuclein and Parkinson disease.
T cells, α-synuclein and Parkinson disease.
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DOI：
10.1016/b978-0-12-819410-2.00023-0
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发表时间：
2022
影响因子：
--
通讯作者：
Sulzer, David
中科院分区：
文献类型：
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作者：
Garretti, Francesca;Monahan, Connor;Sette, Alessandro;Agalliu, Dritan;Sulzer, David
对α-突触核蛋白的自身免疫反应可能参与了这种疾病的发病机制，这一观点源于有报道称，α-突触核蛋白的突变或主要组织相容性复合体的某些等位基因与该病有关，而且中脑中的多巴胺能和去甲肾上腺素能神经元可以呈现抗原表位。在这里，我们讨论了最近的证据，从α-突触核蛋白衍生的一组确定的多肽作为特定的MHC等位基因显示的抗原表位，驱动帕金森病患者的辅助性和细胞毒性T细胞反应。此外，磷酸化的α-突触核蛋白可能以一种限制较少的方式激活帕金森病患者的T细胞反应。虽然获得性免疫系统在疾病发病机制中的作用尚不清楚，但临床前动物模型和体外研究表明，T细胞可能与神经元相互作用，发挥与神经元死亡和神经保护相关的作用。这些发现表明，以T细胞为靶点并改善炎症性肠病或中枢神经系统自身免疫性疾病(如多发性硬化症)的发病率或疾病严重程度的疗法可能对PD有用。
The notion that autoimmune responses to α-synuclein may be involved in the pathogenesis of this disorder stems from reports that mutations in α-synuclein or certain alleles of the major histocompatibility complex (MHC) are associated with the disease and that dopaminergic and norepinephrinergic neurons in the midbrain can present antigenic epitopes. Here, we discuss recent evidence that a defined set of peptides derived from α-synuclein act as antigenic epitopes displayed by specific MHC alleles and drive helper and cytotoxic T cell responses in patients with PD. Moreover, phosphorylated α-synuclein may activate T cell responses in a less restricted manner in PD. While the roles for the acquired immune system in disease pathogenesis remain unknown, preclinical animal models and in vitro studies indicate that T cells may interact with neurons and exert effects related to neuronal death and neuroprotection. These findings suggest that therapeutics that target T cells and ameliorate the incidence or disease severity of inflammatory bowel disorders or CNS autoimmune diseases such as multiple sclerosis may be useful in PD.