Investigation of Neurodegenerative Disorders (I)

Abstract

Metallic elements, especially transition elements, appear to play an important role in neurodegenerative disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Guamanian parkinsonism-dementia complex (PDC) [1-5], based on findings of excessive accumulations of metallic elements in the brains of PDC cases, and iron in idiopathic Parkinson’s disease [6-9]and Alzheimer’s disease [10-11]. The pathogenesis of the disease is still unknown, and researchers have suggested environmental factors as being of etiological importance [12,13]. The “oxidative stress” hypothesis suggests that excessive transition metals can exchange electrons and change their valence, which would promote production of free radicals that cause oxidative damage and neuronal degeneration [14-18]. Oxidative stress is defined as the strain of cellular function induced by reactive oxygen species (ROS), such as superoxide anions (O ⁻₂ ), hydroxyl radicals (OH⁻), hydrogen peroxide (H₂O₂), and peroxynitrite (ONOO⁻) [19]. ROS can induce lethal cellular damage through oxidation and peroxidation of proteins, lipids, and nucleic acids. Details of the relationships between transition metals and neuronal degeneration are still unclear. The distribution and chemical state of these metals is expected to give some insights into the understanding of pathogenic mechanism of these neurodegenerative disorders.