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.
