The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.

中文翻译：

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帕金森病中的多胺：神经毒性和神经保护之间的平衡

多胺腐胺、亚精胺和精胺是在哺乳动物细胞中至关重要的丰富的聚阳离子。它们的细胞水平受到降解和合成以及摄取和输出的严格调节。在这里，我们讨论了帕金森病 (PD) 中多胺的神经保护作用和神经毒性作用之间的微妙平衡。多胺水平随着年龄的增长而下降，并且在帕金森病患者中发生改变，而最近对 ATP13A2 (PARK9) 的机制研究表明，多胺稳态紊乱在帕金森病中具有驱动作用。多胺影响 PD 发病机制中的途径，例如 α-突触核蛋白聚集，并影响 PD 相关过程，例如自噬、重金属毒性、氧化应激、神经炎症和溶酶体/线粒体功能障碍。我们提出了一些突出的研究问题，涉及多胺在帕金森病中的作用、它们作为帕金森病生物标志物的潜力，以及针对多胺稳态的帕金森病可能的治疗策略。