Emerging therapeutic opportunities of novel thiol-amides, NAC-amide (AD4/NACA) and thioredoxin mimetics (TXM-Peptides) for neurodegenerative-related disorders
Emerging therapeutic opportunities of novel thiol-amides, NAC-amide (AD4/NACA) and thioredoxin mimetics (TXM-Peptides) for neurodegenerative-related disorders
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DOI：
10.1016/j.freeradbiomed.2021.08.239
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发表时间：
2021-09-27
影响因子：
7.4
通讯作者：
Atlas, Daphne
中科院分区：
文献类型：
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作者：
Atlas, Daphne
了解神经退行性疾病已经挑战了科学家几十年。很明显，寿命的缩短通常与神经退行性疾病的发展相关。氧化应激和随后的炎症损伤似乎有助于与神经退行性变相关的不同分子和生化机制。在这篇综述中，我研究了新的氨基酸为基础的化合物，包括AD系列（AD 1-AD 7），特别是N-乙酰半胱氨酸酰胺，AD 4，也称为NACA，和系列的硫氧还蛋白模拟（TXM）肽，TXM-CB 3-TXM-CB 16的保护性能。这些抗氧化/抗炎化合物旨在穿过血脑屏障（BBB）并渗透细胞膜，可以有效治疗神经退行性疾病。该综述讨论了这些新试剂所表现出的细胞保护的分子机制，重点关注氧化应激，线粒体应激，炎症损伤和预防过早细胞死亡的逆转。此外，它将涵盖AD 4/ NACA和硫氧还蛋白模拟肽，这是目前正在开发的临床前景的展望。
Understanding neurodegenerative diseases have challenged scientists for decades. It has become apparent that a decrease in life span is often correlated with the development of neurodegenerative disorders. Oxidative stress and the subsequent inflammatory damages appear to contribute to the different molecular and biochemical mechanisms associated with neurodegeneration. In this review, I examine the protective properties of novel amino acid based compounds, comprising the AD series (AD1-AD7) in particular N-acetylcysteine amide, AD4, also called NACA, and the series of thioredoxin mimetic (TXM) peptides, TXM-CB3-TXM-CB16. Designed to cross the blood-brain-barrier (BBB) and permeate the cell membrane, these antioxidant/anti-inflammatory compounds may enable effective treatment of neurodegenerative related disorders. The review addresses the molecular mechanism of cellular protection exhibited by these new reagents, focusing on the reversal of oxidative stress, mitochondrial stress, inflammatory damages, and prevention of premature cell death. In addition, it will cover the outlook of the clinical prospects of AD4/ NACA and the thioredoxin-mimetic peptides, which are currently in development.