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.

Automated summary

Understanding neurodegenerative diseases has been a challenge for scientists for decades, with a decrease in lifespan often linked to the development of these disorders. Oxidative stress and inflammatory damages are key factors contributing to neurodegeneration. Novel amino acid based compounds and thioredoxin mimetic peptides designed to cross the blood-brain-barrier show potential for effective treatment of neurodegenerative diseases by reversing oxidative stress, mitochondrial stress, inflammatory damages, and preventing premature cell death. Perspectives on the clinical prospects of these compounds are discussed in this review.