Antioxidants: A New Therapy for Neurodegenerative Diseases?

Introduction

Neurodegenerative diseases—such as Alzheimer disease, Parkinson disease, and Huntington disease—affect millions of people worldwide and the quest to find effective treatments is ongoing. These disorders are often caused by mitochondrial malfunction and the reactive oxygen species (ROS) that are subsequently produced.

Neurotoxicity and cell death can also be caused by excitotoxicity, synaptic dysfunction, impaired protein degradation systems, endoplasmic reticulum stress, DNA damage, inflammation, and cell cycle reentry. The long list of possible causes is why it is so difficult for researchers to find a cure for these progressive diseases.

However, many researchers are taking their strategies in a new direction by looking into antioxidant treatment as a possible intervention. One of the major concerns with neurodegenerative diseases is the substantial increase in ROS. Researchers are hopeful that by introducing antioxidant molecules, the oxidative equilibrium will be reset.

Researchers from Spain and the United Kingdom recently published a review of current efforts in this area in the International Journal of Molecular Sciences. In it, they review mechanisms and drugs of most interest.

Key Findings

Because the brain is highly vulnerable to oxidative stress, decreasing the amount of ROS being produced could be critical. Antioxidants are capable of converting highly destructive free radicals and nonradical molecules, thereby reducing cerebral stress. These antioxidants can be enzymatic, non-enzymatic, endogenous, and exogenous. Although they do not all work in the same mechanisms, they all work to defend the brain from degeneration.

The most common types of agents involved in testing around the world include exogenous antioxidants, which include polyphenols, carotenes, and vitamins. However, researchers are taking a closer look at different hormones, such as melatonin, because of their neuroprotective properties. The latest randomized trial included antioxidants such as resveratrol, carotenoids, omega-3 fatty acids, vitamin E, and melatonin in patients with Alzheimer disease.

Each of these different substances have various effects on their potential improvement of neurodegenerative diseases. Resveratrol has antioxidant, anti-inflammatory, and neuroprotective abilities and when combined with donepezil, can help increase patients’ inflammatory response.

Carotenoids in combination with omega-3 fatty acid and vitamin E have seemed to improve active memory in older patients. Melatonin is the newest addition to clinical trials and researchers are hopeful it will help patients with Alzheimer disease with non-rapid eye movement sleep.

Limitations

The researchers have faced many limitations while searching for a possible drug contender due to the fact that the clinical trials failed. Many show reports of the antioxidant treatment having no serious improvements in the patients’ symptoms. Environmental factors such as exercise and diet could also play a role in these unpromising results.

Conclusion

Researchers all over the world are taking part in the quest to find treatment options for neurodegeneration diseases, including Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic later sclerosis, and traumatic brain injury. Many of them are diving into the world of using antioxidant agents, one of the most being melatonin. The use of melatonin and other related antioxidant treatments is still in its early phases but could hold a promising future for neurogenerative disease.

About the Author

Christina Nault is a 2025 PharmD candidate at the University of Connecticut

Reference

Morén C, deSouza RM, Giraldo DM, Uff C. Antioxidant Therapeutic Strategies in Neurodegenerative Diseases. Int J Mol Sci. 2022;23(16):9328. Published 2022 Aug 19. doi:10.3390/ijms23169328