Role of reactive oxygen species in the neurotoxicity of environmental agents implicated in Parkinson's disease

Abstract

Among age-related neurodegenerative diseases, Parkinson's disease (PD) represents the best example for which oxidative stress has been strongly implicated. The etiology of PD remains unknown, yet recent epidemiological studies have linked exposure to environmental agents, including pesticides, with an increased risk of developing the disease. As a result, the environmental hypothesis of PD has developed, which speculates that chemical agents in the environment are capable of producing selective dopaminergic cell death, thus contributing to disease development. The use of environmental agents such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone, paraquat, dieldrin, and maneb in toxicant-based models of PD has become increasingly popular and provided valuable insight into the neurodegenerative process. Understanding the unique and shared mechanisms by which these environmental agents act as selective dopaminergic toxicants is critical in identifying pathways involved in PD pathogenesis. In this review, we discuss the neurotoxic properties of these compounds with specific focus on the induction of oxidative stress. We highlight landmark studies along with recent advances that support the role of reactive oxygen and reactive nitrogen species from a variety of cellular sources as potent contributors to the neurotoxicity of these environmental agents. Finally, human risk and the implications of these studies in our understanding of PD-related neurodegeneration are discussed.

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…Rotenone disrupts the mitochondrial electron-transport chain at complex I and causes acute ATP depletion and generation of massive ROS (Drechsel and Patel, 2008). This study has demonstrated the protective effect of hyperforin on attenuating rotenoneinduced cytotoxicity in differentiating CG-4 cells.…”

Tearful relations: oxidative stress, inflammation and eye diseases

“…A cell is able to overcome small perturbations and regain its original state; however, more severe oxidative stress can cause cell death, and even moderate oxidation can trigger apoptosis, while more intense stresses may causes necrosis (8) . SOD is one of the main antioxidant systems and is made up of three components: CuZn-SOD (SOD1) exists in the cytosol, Mn-SOD (SOD2) in the mitochondrial matrix, and extracellular SOD (SOD3) in the tissue as the secretory form (9) . Because the superoxide anion radical substrate poorly penetrates membranes, the SOD isoenzymes primarily exert their protective functions in their respective compartments.…”

Therapeutic and Diagnostic Agents for Parkinson's Disease

“…Factors There is evidence to suggest that environmental toxicants may cause some parkinsonism syndromes [72,73]. This hypothesis seems consistent with the fact that PD is now the second most common degenerative neuropsychiatric disorder (after the dementias), in contrast to its evident rarity in previous centuries [74].…”