Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease.

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Society transactions Pub Date : 2024-06-26 DOI:10.1042/BST20231290
Dale D O Martin, Shaun S Sanders
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引用次数: 0

Abstract

Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes in the dynamic addition of saturated fatty acids to proteins, a process known as S-acylation. With the advent of new techniques to study S-acylation and the recent discovery of new enzymes that facilitate protein deacylation, novel small molecules are emerging as potential new therapeutic treatments. Huntington disease (HD) is a devastating, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric deficits caused by a CAG repeat expansion in the HTT gene. The protein that is mutated in HD, huntingtin, is less S-acylated which is associated with mutant HTT aggregation and cytotoxicity. Recent exciting findings indicate that restoring S-acylation in HD models using small molecule inhibitors of the deacylation enzymes is protective. Herein, we set out to describe the known roles of S-acylation in HD and how it can be targeted for therapeutic design.

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让我们胖起来:S-酰化成为亨廷顿病的治疗靶点。
无论病因如何,蛋白质错位都是神经变性的关键第一步,它与蛋白质中饱和脂肪酸的动态添加变化有关,这一过程被称为 S-酰化。随着研究 S-酰化的新技术的出现,以及最近发现促进蛋白质脱酰化的新酶,新型小分子药物正在成为潜在的新疗法。亨廷顿病(Huntington disease,HD)是一种毁灭性的致命神经退行性疾病,其特征是由 HTT 基因中的 CAG 重复扩增引起的运动、认知和精神障碍。在 HD 中发生突变的亨廷蛋白的 S-酰化程度较低,这与突变 HTT 的聚集和细胞毒性有关。最近令人兴奋的研究结果表明,使用脱乙酰化酶的小分子抑制剂恢复 HD 模型中的 S-乙酰化具有保护作用。在此,我们将介绍S-酰化在HD中的已知作用,以及如何将其作为治疗设计的靶点。
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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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