突变的亨廷顿蛋白在转录和翻译后水平上扰乱了亨廷顿病中的半胱氨酸代谢。

Paul Bindu D, Sbodio Juan I, Snyder Solomon H

Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Antioxidants (Basel). 2022 Jul 27;11(8):1470. doi: 10.3390/antiox11081470.

Cysteine is a semi-essential amino acid that not only plays an essential role as a component of protein synthesis, but also in the generation of numerous sulfur-containing molecules such as the antioxidant glutathione and coenzyme A. We previously showed that the metabolism of cysteine is dysregulated in Huntington's disease (HD), a neurodegenerative disorder triggered by the expansion of polyglutamine repeats in the protein huntingtin. In this study, we showed that cysteine metabolism is compromised at multiple levels in HD, both transcriptional and post-translational. Accordingly, restoring cysteine homeostasis may be beneficial in HD.

半胱氨酸是一种半必需氨基酸，它不仅作为蛋白质合成的组成部分发挥重要作用，而且在生成众多含硫分子（如抗氧化剂谷胱甘肽和辅酶A）方面也发挥着重要作用。我们之前表明，在亨廷顿病（HD）中半胱氨酸代谢失调，HD是一种由亨廷顿蛋白中多聚谷氨酰胺重复序列扩增引发的神经退行性疾病。在本研究中，我们表明在HD中半胱氨酸代谢在转录和翻译后多个水平上受到损害。因此，恢复半胱氨酸稳态可能对HD有益。