Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection.

IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Annual review of biochemistry Pub Date : 2023-06-20 DOI:10.1146/annurev-biochem-071322-021330
Stephanie Vrijsen, Marine Houdou, Ana Cascalho, Jan Eggermont, Peter Vangheluwe
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引用次数: 4

Abstract

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.

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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、亚精胺和精胺是哺乳动物细胞中非常重要的多聚体。它们的细胞水平受到降解和合成以及吸收和输出的严格调节。在这里,我们讨论在帕金森病(PD)的背景下多胺的神经保护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,PD患者的多胺水平也会发生改变,而最近对ATP13A2 (PARK9)的机制研究表明,多胺稳态紊乱在PD中起着驱动作用。多胺影响PD发病途径,如α-突触核蛋白聚集,并影响PD相关过程,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。我们就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提出了突出的研究问题。
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来源期刊
Annual review of biochemistry
Annual review of biochemistry 生物-生化与分子生物学
CiteScore
33.90
自引率
0.00%
发文量
31
期刊介绍: The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.
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