Sphingolipids and impaired hypoxic stress responses in Huntington disease

IF 14 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Progress in lipid research Pub Date : 2023-04-01 DOI:10.1016/j.plipres.2023.101224

Johannes Burtscher , Giuseppe Pepe , Niran Maharjan , Nathan Riguet , Alba Di Pardo , Vittorio Maglione , Grégoire P. Millet

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引用次数: 1

Abstract

Huntington disease (HD) is a debilitating, currently incurable disease. Protein aggregation and metabolic deficits are pathological hallmarks but their link to neurodegeneration and symptoms remains debated.

Here, we summarize alterations in the levels of different sphingolipids in an attempt to characterize sphingolipid patterns specific to HD, an additional molecular hallmark of the disease. Based on the crucial role of sphingolipids in maintaining cellular homeostasis, the dynamic regulation of sphingolipids upon insults and their involvement in cellular stress responses, we hypothesize that maladaptations or blunted adaptations, especially following cellular stress due to reduced oxygen supply (hypoxia) contribute to the development of pathology in HD. We review how sphingolipids shape cellular energy metabolism and control proteostasis and suggest how these functions may fail in HD and in combination with additional insults. Finally, we evaluate the potential of improving cellular resilience in HD by conditioning approaches (improving the efficiency of cellular stress responses) and the role of sphingolipids therein.

Sphingolipid metabolism is crucial for cellular homeostasis and for adaptations following cellular stress, including hypoxia. Inadequate cellular management of hypoxic stress likely contributes to HD progression, and sphingolipids are potential mediators. Targeting sphingolipids and the hypoxic stress response are novel treatment strategies for HD.

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亨廷顿病的鞘脂和缺氧应激反应受损

亨廷顿病(HD)是一种使人衰弱的，目前无法治愈的疾病。蛋白质聚集和代谢缺陷是病理特征，但它们与神经变性和症状的联系仍存在争议。在这里，我们总结了不同鞘脂水平的变化，试图表征HD特有的鞘脂模式，这是该疾病的另一个分子标志。基于鞘脂在维持细胞内稳态中的关键作用，鞘脂在损伤时的动态调节及其参与细胞应激反应，我们假设适应不良或适应钝化，特别是由于氧气供应减少(缺氧)导致的细胞应激导致HD的病理发展。我们回顾了鞘脂如何塑造细胞能量代谢和控制蛋白质平衡，并提出了这些功能如何在HD中失效，并结合其他损害。最后，我们评估了通过调节方法(提高细胞应激反应的效率)改善HD细胞弹性的潜力以及鞘脂在其中的作用。鞘脂代谢对细胞内稳态和细胞应激(包括缺氧)后的适应至关重要。缺氧应激的细胞管理不足可能导致HD的进展，鞘脂是潜在的介质。针对鞘脂和低氧应激反应是治疗HD的新策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in lipid research 生物-生化与分子生物学

CiteScore

24.50

自引率

2.20%

发文量

审稿时长

14.6 weeks

期刊介绍： The significance of lipids as a fundamental category of biological compounds has been widely acknowledged. The utilization of our understanding in the fields of biochemistry, chemistry, and physiology of lipids has continued to grow in biotechnology, the fats and oils industry, and medicine. Moreover, new aspects such as lipid biophysics, particularly related to membranes and lipoproteins, as well as basic research and applications of liposomes, have emerged. To keep up with these advancements, there is a need for a journal that can evaluate recent progress in specific areas and provide a historical perspective on current research. Progress in Lipid Research serves this purpose.