Professor of Neurochemistry, Dept. of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
Free Radic Biol Med. 2021 Nov 20;176:120-141. doi: 10.1016/j.freeradbiomed.2021.08.239. Epub 2021 Sep 1.
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.
理解神经退行性疾病几十年来一直是科学家们面临的挑战。很明显，寿命的缩短通常与神经退行性疾病的发展有关。氧化应激和随后的炎症损伤似乎与神经退行性变相关的不同分子和生化机制有关。在这篇综述中，我检查了新型基于氨基酸的化合物的保护特性，包括 AD 系列（AD1-AD7），特别是 N-乙酰半胱氨酸酰胺、AD4，也称为 NACA，以及一系列硫氧还蛋白模拟物（TXM）肽，TXM-CB3-TXM-CB16。这些抗氧化剂/抗炎化合物旨在穿过血脑屏障（BBB）并穿透细胞膜，可能能够有效治疗与神经退行性相关的疾病。该综述介绍了这些新试剂表现出的细胞保护的分子机制，重点是逆转氧化应激、线粒体应激、炎症损伤和预防细胞过早死亡。此外，它还将涵盖 AD4/NACA 和正在开发中的硫氧还蛋白模拟肽的临床前景展望。
