Parkinson's disease (PD) devastates 6.3 million people, ranking it as one of the most prevalent neurodegenerative motor disorders worldwide. PD patients may manifest symptoms of postural instability, bradykinesia, and resting tremors as a result of increasing α-synuclein aggregation and neuron death with disease progression. Therapy options are limited, and those available to patients may worsen their condition. Thus, investigations to understand disease progression may help develop therapeutic strategies for improvement of quality of life for patients suffering from PD. This review provides an overview of α-synuclein, a presynaptic neuronal protein whose function in the healthy brain and PD pathology remains a mystery. This review also focuses on calcium-induced activation of calpain, a neutral protease, and the subsequent cascade of cellular processing of α-synuclein and emerging defense responses observed in experimental models of PD: microglial activation, dysregulation of T cells, and inflammatory responses in the brain. In addition, this review discusses the events of cross presentation of synuclein peptides by professional antigen presenting cells and microglia, induction of inflammatory responses in the periphery and brain, and emerging calpain-targeted therapeutic strategies to attenuate neuronal death in PD.

帕金森病 (PD) 造成 630 万人死亡，是全球最常见的神经退行性运动障碍之一。随着疾病进展，α-突触核蛋白聚集增加和神经元死亡，PD 患者可能会出现姿势不稳、运动迟缓和静息性震颤等症状。治疗选择有限，患者可用的治疗可能会使病情恶化。因此，了解疾病进展的研究可能有助于制定改善帕金森病患者生活质量的治疗策略。本综述概述了 α-突触核蛋白，这是一种突触前神经元蛋白，其在健康大脑和 PD 病理学中的功能仍然是个谜。本综述还重点关注钙诱导的钙蛋白酶（一种中性蛋白酶）激活，以及随后的 α-突触核蛋白细胞加工级联，以及 PD 实验模型中观察到的新兴防御反应：小胶质细胞激活、T 细胞失调和炎症反应。大脑。此外，这篇综述还讨论了专业抗原呈递细胞和小胶质细胞交叉呈递突触核蛋白肽的事件、外周和大脑炎症反应的诱导，以及减少帕金森病中神经元死亡的新兴钙蛋白酶靶向治疗策略。