Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain areas. The detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear, and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in PD. However, the formation of α-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD, possibly stemming from the consequence of protein misfolding and dysfunctional proteostasis. Proteostasis is the mechanism for maintaining protein homeostasis via modulation of protein translation, enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and autophagy. Deregulated protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes, leading to pathological protein aggregation and neurodegeneration in PD. In recent years, multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been identified. The potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

中文翻译：

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分子靶标调节对帕金森氏病中蛋白质稳定和神经元变性至关重要的蛋白质翻译

帕金森氏病（PD）是最常见的神经退行性运动障碍，其特征是黑质致密部中的多巴胺能神经元逐渐丧失，并在受影响的大脑区域形成路易体。PD中多巴胺能神经元选择性丢失的详细致病机制尚不清楚，并且尚未开发出缓解PD中进行性多巴胺能神经元变性的药物或治疗方法。然而，已经确定路易体中α-突触核蛋白阳性蛋白聚集体的形成是PD的常见病理特征，可能是由于蛋白错误折叠和蛋白稳态失调所致。蛋白质稳态是通过调节蛋白质翻译来维持蛋白质稳态的机制，泛素蛋白酶体系统和自噬功能可增强分子伴侣的能力，并迅速清除错误折叠的蛋白质。蛋白质翻译失调和分子伴侣的能力受损或蛋白质降解会干扰蛋白稳态过程，导致PD中的病理性蛋白质聚集和神经变性。近年来，在蛋白质翻译调控中对蛋白质稳定和多巴胺能神经元变性至关重要的多个分子靶标已被确定。这些分子靶标对PD的神经退行性病变的潜在病理生理和治疗意义突出。导致PD中的病理性蛋白质聚集和神经退行性变。近年来，在蛋白质翻译调控中对蛋白质稳定和多巴胺能神经元变性至关重要的多个分子靶标已被确定。这些分子靶标对PD的神经退行性病变的潜在病理生理和治疗意义突出。导致PD中的病理性蛋白质聚集和神经退行性变。近年来，在蛋白质翻译调控中对蛋白质稳定和多巴胺能神经元变性至关重要的多个分子靶标已被确定。这些分子靶标对PD的神经退行性病变的潜在病理生理和治疗意义突出。