Can oxidative stress shrink your brain?

With baby boomers growing older, the age of the population in the United States is increasing. About 50 million Americans are affected each year by over 600 neurodegenerative diseases. Neurodegenerative disease refers to conditions in which nerve cells progressively degenerate and/or die.  The most common neurodegenerative disorders are Alzheimer’s disease and Parkinson’s disease.

Figure 1. Oxidative stress can initiate a cascade that leads to cell death.

Figure 1. Oxidative stress can initiate a cascade that leads to cell death.

Neural decay and ageing related with these diseases increases with oxidative stress. A primary source of oxidative stress is reactive oxygen species (ROS). Some of these molecules are free radicals, all are highly reactive and destructive if present in excess. Mitochondria make most of the ROS found in the body during ATP production. ROS are also created when the enzyme monoamine oxidase (MAO) beginsthe oxidation of biogenic amine neurotransmitters (e.g. dopamine and serotonin).

In Parkinson’s disease, oxidative stress leads to a cascade of events that underlie the neural decay associated with this disease (Figure 1). Oxidative stress leads to mitochondrial abnormalities, which contributes to excitotoxicity. Excitotoxicity leads to protein accumulation and inflammation, which ultimately results in cellular damage and death. Excitotoxicity that leads to the death of neurons in termed neurotoxicity.

Neurotoxicity is seen in other neurodegenerative diseases as well. Normally, excitatory neurotransmission is essential for synaptic development and plasticity, as well as learning and memory. However, too much stimulation of glutamatergic receptors, the most excitatory in the central nervous system, induces neurotoxicity. This neurotoxicity contributes to neural cell damage. Hyperactivation of the AMPA-type glutamate receptors also creates oxidative stress that can contribute to neurodegeneration.

Assessing oxidative stress and neurotransmitters, specifically glutamate, can help identify therapy options that may help reduce or slow neurodegeneration.

References:
http://www.neurodegenerationresearch.eu/about/what/
Melo, A., et al. (2011). Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Therapeutic Perspectives. Oxidative Medicine and Cellular Longevity, 1-14.
Uttara, B., et al. (2009). Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Curr Neuropharmacol, 7(1): 65-74.
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