Oxygen: Parkinson’s, Alzheimer’s, Huntington’s

Parkinson’s, Alzheimer’s, and Huntington’s are degenerative brain diseases with some similarities in symptoms. Oxidative stress has been linked to these diseases, but causation is unproven. Dementia is a central feature but is not diagnostic. Based on historical, clinical descriptions the order of discovery as a disease is: Parkinson’s (1817), Huntington’s (1842) although it probably has been known since the Middle Ages and was called “chorea”, and Alzheimer’s (1906). Alzheimer’s is the most common; Parkinson’s is second; and Huntington’s is the third most common neuronal, degenerative disease. None of these diseases can be cured, and there is generally a long, severe decline in functional ability that is tragic for the individual, the family and friends. Although the causes of these diseases are unknown, there are genetically inherited risks for each. The pathophysiology, brain sites affected, cellular and subcellular mechanisms, and genetics for each disease is complex and oxidant stress has been incriminated for some aspects of these diseases. Parkinson’s results in a progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the metabolism of dopamine itself generates reactive oxygen species. Therapy with the dopamine precursor levo-dopa (dopamine does not pass the blood- brain barrier) does not provide lasting benefits. Speculation that Parkinson’s disease is caused by reactive oxygen species generated from pesticide exposure has not been proven. Discoveries by co-workers in my laboratory pointing to special sensitivity from oxidant stress for certain iron-containing enzymes in amino acid metabolism are promising links to oxidant stress causation. Generation of oxidant stress via aberrant mitochondrial oxidative metabolism is a viable thesis but a cure for these diseases is not in sight and is more likely to result from future discoveries using stem cells and perhaps gene therapy.

Keywords: Age-related neurodegeneration, α-synuclein, Alzheimer’s, β-amyloid deposits, Cellular redox balance, Dopamine, Gene mutation, Huntingtin gene, Huntingtin protein, Huntington’s, Kynurenic acid, Kynurenine pathway, Levodopa, Lewy bodies, Miss-folded proteins, Oxidant stress, Parkinson’s, Protein phosphorylation, Quinolinic acid, ROS, Tau, Tryptophan metabolism.