Understanding Parkinson's Disease
Overview
Introduction to Parkinson's Disease
Oxidative Damage and Parkinson's Disease
Oxidative damage in Mitochondria
Parkinson's disease is the second most common neurodegenerative disease. It effects 1.5 million Americans, but its cause is as of yet unknown. This report examines possible hypotheses of the cause of Parkinson's. Specifically, I will explore oxidative damage to mitochondria as a cause of the death of neurons. A biochemical analysis of oxidative damage in mitochondria, reported by Murray et. al. (2003), is described.
A decrease in the the neurotransmitter dopamine is seen on positron emission tomography (PET) of the brain as the disease progresses. (Red indicates high levels of dopamine, blue low levels of dopamine.) Ottley et. al, 1999. Reprinted with permission.Overview
Parkinson's disease is a neurodegenerative disease, in which there is death of neurons that produce the neuronal signaling molecule dopamine. The depletion of dopamine causes a person to have motor skill problems, such as resting tremors, slowness of movement, rigidity, flexed posture, and "freezing." These symptoms can be temporarily treated by the administration of drugs that can replace dopamine. However, as the disease progresses the treatments often stop working, and other symptoms such as depression, lack of motivation, passivity, and even dementia may develop. The cause of this disease is unknown, despite much research of the subject.Because Parkinson's often develops sporadically in older people, one hypothesis of its cause involves the accumulation of oxidative damage to mitochondria, the energy producing organelles of the cell, which then causes death of the cell. Murray et. al. (2003) have recently shown that peroxynitrite (ONOO-), a dangerous oxidant which can form spontaneously in mitochondria, can cause damage to and inhibit electron transport proteins that are involved in aerobic respiration and thus cellular energy generation. They also used mass spectrometry and two-dimensional gel electrophoresis to identify sites of oxidative damage of complex I, the damage of which is a feature of Parkinson's disease. These specific sites can now be used as markers of oxidative damage, and to determine the role oxidative damage may have in neurodegenerative diseases.
Created by: Zaneta Navratilova, zanetan@email.arizona.edu, as an honors project for biochemistry 462b, instructor: Dr. Don P. Bourque, University of Arizona
Last updated: May 10, 2004
