Multiple antioxidants in the prevention and treatment of neurodegenerative disease: analysis of biologic rationale

Abstract

Parkinson's disease and Alzheimer's disease are major progressive neurologic disorders, the risk of which increases with advancing age (65 years and over). In familial cases, however, early onset of disease (35-65 years) is observed. In spite of extensive basic and chemical research on Parkinson's disease and Alzheimer's disease, no preventive or long-term effective treatment strategies are available. The analysis of existing literature suggests that oxidative stress is a major intermediary risk factor for the action of diverse groups of neurotoxins that are involved in these neurodegenerative diseases. In this review, it is proposed that the epigenetic components (mitochondria, other organelles, membranes, protein modification) rather than nuclear genes of neurons are the primary targets for the action of neurotoxins, including free radicals. In addition, a scientific rationale for using multiple antioxidants in clinical trials for the prevention of Parkinson's disease and Alzheimer's disease among high-risk populations, and as an adjunct to standard therapy in the treatment of these diseases is presented.

Will a Healthy Lifestyle Help Prevent Alzheimer's Disease?

“…Third, many of the supplements taken by individuals and used in clinical trials differ in their ingredients. For example, the vitamin E supplements used in intervention studies have largely been made from synthetic vitamin E, which frequently includes only the alpha-tocopherol form of vitamin E. Other tocopherols may be more efficient in crossing the blood-brain barrier (70). Fourth, the older age and disease state of the subjects in many studies may be associated with neurologic damage that is too great for increases in antioxidant intake to stabilize or improve the condition.…”

A Macrophage−Nanozyme Delivery System for Parkinson's Disease

“…Such inflammatory activities are profound, as they lead to excessive production of pro-inflammatory products and reactive oxygen species (ROS) that lead in part, to cell death and neurodegen-eration. We posit that by affecting neuroinflammatory activities during disease, such as through the use of targeted antioxidants or drugs that inhibit the production or formation of pro-inflammatory cytokines and eicosanoids, the levels of ROS as well as other neurotoxins could be reduced, resulting in improved disease outcomes (13). However, such approaches have been limited, as drugs must not only penetrate the BBB but also find themselves in sufficient concentrations to affect ongoing disease mechanisms.…”

Protective Activity of Aromatic Amines and Imines against Oxidative Nerve Cell Death

“…Nevertheless, results from standardized animal models, epidemiological studies, and from a wide array of biochemical considerations seem to indicate that certain investigational antioxidant compounds might have a profound preventive or therapeutic value (Sies, 1993;Baker et al, 1998;Parkes et al, 1998;Reiter, 1998;Leppala et al, 1999;Nourhashemi et al, 2000;Jung et al, 2001; and the above reviews). Consequently, the search for antioxidant pharmaceuticals which (i) inhibit pathogenetically relevant oxidative phenomena, (ii) readily pass the blood-brain barrier, and (iii) show a higher efficacy per dose, thereby concomitantly exhibiting a reduced risk of adverse side effects, is in the center of interest of clinically involved physicians as well as biochemically focused scientists (Harman, 1996;Behl, 1999;Prasad et al, 1999;Alexi et al, 2000;Grunblatt et al, 2000;Prasad et al, 2000;Sramek and Cutler, 2000;Wolozin and Behl, 2000;Gilgun-Sherki et al, 2001).…”