Emerging therapeutic opportunities of novel thiol-amides, NAC-amide (AD4/NACA) and thioredoxin mimetics (TXM-Peptides) for neurodegenerative-related disorders

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. [Display omitted] •N-acetylcysteine amide (AD4/NACA) and thioredoxin mimetic (TXM) peptides protect the cells from oxidative stress damages.•TXM peptides and AD4/NACA permeate the cell membrane and cross the BBB, scavenging ROS and restoring GSH.•TXM peptides and AD4/NACA inhibit phosphorylation of the mitogen activated protein kinases p38 MAPK and JNK1/2.•TXM-peptides and AD4/NACA inhibit nuclear translocation of NF-κB and protect the cells from inflammatory damages.•TXM-peptides and AD4/NACA are non-toxic and suited for treating degenerative and neurodegenerative diseases.