Oxidative Stress in Neurodegenerative Diseases:

Parkinson's disease and Alzheimer's disease

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Parkinson’s disease is the most common neurodegenerative movement disorder and the second most common neurodegenerative disease in developed countries. This disease is characterized by a loss of dopamine neurons in the Substantia nigra that are needed for proper motor function. As a result, those who suffer from this disorder develop tremors and muscle rigidity.

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In “Calcium, Cellular Aging, and Selective Neuronal Vulnerability inParkinson’s Disease,” D. James Surmeier and his colleagues focused on the dopamine neurons of the Substantia nigra (SNc DA Neurons) and why they die. It is hypothesized that the primary factor for their deaths is stress created by sustained Calcium entry which leads to compromised oxidative defenses, amongst other injuries. Also, reactive oxygen species (ROS) are easily converted into free radicals which are chemical species that have unpaired electrons in their outer orbit. They can be harmful by causing mutations in SNc DA neurons which can trigger neuron degeneration and apoptosis. Parkinson’s disease is thought to be a result of this accelerated aging and oxidative stress in selective neural systems.

Oxidative Stress:

     A similar hypothesis concerning oxidative stress was made by Manuela Padurariu and her colleagues with regards to Alzheimer’s disease. In general, oxidative-stress-related injuries are caused by an imbalance between pro-oxidants and anti-oxidants. Specifically, an excess of pro-oxidant compounds triggers antioxidant defenses that deplete the body’s antioxidant reserves through reduction of the antioxidants to harmful free radicals. These free radicals can attack cellular structures such as DNA, RNA, proteins, and lipids in the cellular membrane. Less aggressive free radicals cause easily repairable lesions, but more aggressive types can be mutagenic and highly cytotoxic. In turn, oxygen radicals can cause cancer and neurological diseases such as Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease.

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     The brain is especially vulnerable to oxidative stress because of its low levels of antioxidants, high concentration of the lipids free radicals attack via lipidic peroxidation, and its high biochemical oxygen demand. The most vulnerable areas in the brain are in the hippocampus, a highly active part of the brain. This is because the most active neurons already have intrinsic oxidative stress due to their high bioenergetics needs and, therefore, they have a greater number of mitochondria that are vulnerable to additional oxidative stress. An accumulation of ROS in Alzheimer’s disease may be the earliest sign of risk of developing the disease. Theories about the accumulation of ROS in Alzheimer’s disease relate to dysfunctions in the mitochondria that lead to the production of more ROS and amyloid beta plaques – a characteristic of Alzheimer’s disease – which activates microglia and leads to more ROS. Also, an overconsumption of antioxidants is thought to lead to the reduction of these antioxidants to free radicals, resulting in a positive feedback loop. Although the mitochondria’s role in Alzheimer’s disease is not fully understood yet, it is thought to be the central cause.

Antioxidant Therapy:

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     Antioxidant compounds may help reduce amyloid beta toxicity. Blueberries, melatonin, Gingko biloba extracts and other supplements contain these antioxidant compounds. The most important soluble antioxidant is Vitamin C because it neutralizes ROS before lipidic peroxidation can occur. Vitamin E also protects membrane lipids from lipidic peroxidation. While these antioxidants may assist in treatment and prevention of Alzheimer’s disease, further research regarding this type of therapy is needed (especially in early stages of Alzheimer’s type dementia) to prove that there is a clear benefit. With the help of biomarkers and more research on the effects of oxidative stress in age-related neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, more treatment options and prevention techniques may become available.

Sources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3235732/pdf/nihms168524.pdf

http://www.hdbp.org/psychiatria_danubina/pdf/dnb_vol25_no4/dnb_vol25_no4_401.pdf

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