Insights into the Disappointing Clinical Trials of Antioxidants in Neurodegenerative Diseases

Abstract

Oxidative stress plays a vital role in the pathogenesis of neurodegenerativediseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The recent excellent article by Kamat et al. published in Journal of Alzheimer’s Disease [1] provided a comprehensive review on the current status of antioxidant therapy for neurodegenerative diseases and analyzed the disappointing clinical trials. In fact, in recent years failures of antioxidants in clinic trials for many other diseases caused by oxidative stress, such as cancer and cardiovascular diseases, have been widely reported [2,3]. Thus, it is of significance to explore the potential reasons why antioxidants have failed in clinical trials. We agree well with Kamat et al.’s opinion that the negative clinical trials do not disprove the pathogenic role of oxidative stress in neurodegenerative diseases [1]. However, besides the possible reasons provided by Kamat et al. [1], we propose some more basic factors, including the intrinsic features of antioxidants and heterogeneity of biological