Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.,ACS Chemical Neuroscience

当前位置： X-MOL 学术 › ACS Chem. Neurosci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of a Novel Oleic Acid Analog with Protective Effects in Multiple Cellular Models of Friedreich Ataxia.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-08-11 , DOI: 10.1021/acschemneuro.0c00323
M Grazia Cotticelli _{1,

2} , Roberto Forestieri ₃ , Shujuan Xia _{1,

2} , Sipak Joyasawal ₄ , Taehee Lee _{1,

2} , Kexin Xu ₄ , Amos B Smith Iii ₃ , Donna M Huryn _{3,

4} , Robert B Wilson _{1,

2,

5}

Affiliation

Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder for which there is no cure or approved treatment. It is characterized by the loss or impaired activity of frataxin protein, which is involved in the biogenesis of iron–sulfur clusters. Our previous studies suggested that cell death in FRDA may involve ferroptosis, an iron-dependent form of cell death requiring lipid peroxidation. Based on reports that oleic acid acts as a ferroptosis inhibitor, we evaluated whether it, other fatty acids, and fatty acid derivatives could rescue viability in cellular models of FRDA. We identified a trifluoromethyl alcohol analog of oleic acid that was significantly more potent than oleic acid itself. Further evaluation indicated that the effects were stereoselective, although a specific molecular target has not yet been identified. This work provides a potential starting point for therapeutics to treat FRDA, as well as a valuable probe molecule to interrogate FRDA pathophysiology.

中文翻译：

在弗里德里希共济失调的多个细胞模型中具有保护作用的新型油酸类似物的鉴定。

腓特烈共济失调（FRDA）是一种遗传性神经退行性疾病，目前尚无治愈或获准的治疗方法。它的特征在于frataxin蛋白的丧失或受损，这与铁硫簇的生物发生有关。我们以前的研究表明，FRDA中的细胞死亡可能与铁减少有关，这是铁依赖的细胞死亡形式，需要脂质过氧化作用。基于关于油酸充当肥大症抑制剂的报道，我们评估了它，其他脂肪酸和脂肪酸衍生物是否可以拯救FRDA细胞模型中的生存能力。我们确定了油酸的三氟甲醇类似物，其效力远高于油酸本身。进一步的评估表明，尽管尚未确定特定的分子靶标，但其作用是立体选择性的。

更新日期：2020-09-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11