Friday, July 22, 2011

Is it Possible that Brain Cells Abandon Mitochondria in Parkinson’s?

Parkinson's disease affects nearly five million individuals today by degenerating brain cells and by damaging nerve cells that control their muscles. In PD, there are neurons in an area of the brainstem called substantia nigra which means “large black area.” It is named for the dark pigment that neurons release as a by-product from synthesizing dopamine. When neurons degenerate, less dopamine reaches neurons’ synapses. The decrease in dopamine causes the poor motor symptoms of Parkinson’s disease. No treatments can cure or slow the course of PD, but replacing or enhancing use of dopamine can temporarily alleviate symptoms.

Recently researchers are reporting that the causes of Parkinson’s are because brain cells are abandoning mitochondria. First, it is important to know that mitochondria uses it’s DNA and ribosome’s to synthesize some of its own proteins. Mitochondria make usable energy for the cell and are often called the “powerhouses”. All cells require energy to grow and move. All cells can access energy for cellular processes by breaking down organic molecules and transferring that energy to a molecule called ATP. Mitochondria produce ATP by extracting energy from substrates. ATP is used by enzymes to perform a wide range of cellular functions. For example, our respiratory and circulatory systems deliver oxygen to the tissues to be used by mitochrondri and to eliminate carbon dioxide. Enzymes within the mitochondria’s membranes are designed to oxidize the substrates. Mitochondria are surrounded by two membranes: an outer and an inner membrane. This creates several different locations that can be used for different functions during the breakdown of organic molecules. Ultimately, in the matrix of the mitochondria the Kreb’s cycle takes place and the electron transport chain happens in the inner membrane.

Researcher, Clemens Scherzer, believes that neurons “divorce” their mitochondria which may cause Parkinson’s. Studies show that by targeting a specific gene set during the beginning stages of PD could slow or halt further damage. PGC-1alpha gene is found to be the most effective master regulator. “PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,” said Scherzer. Medications for diabetes also activate PGC-1alpha making it easier for future Parkinson fighting drugs to be developed. Drugs capable of targeting PGC-1alpha in the brain would be a huge benefit to PD patients if given early on, before too many dopamine neurons die.

Scherzer examined gene activity and identified gene sets from substantia nigra samples of deceased Parkinson’s patients. Ten gene sets were identified to be linked to Parkinson’s and had PGC-1alpha in common, making it clear that it’s the master regulator gene. All ten gene sets should have had proteins responsible for mitochondri to carry out correct cellular functions. However, the genes showed that they were suppressed which caused damage to brain energy metabolism, leading to Parkinson’s. Past studies have said that only one of the five gene complexes had to malfunction in order to cause Parkinson’s. However, Scherzer’s findings showed otherwise, all complexes used to build up the mitochondria’s electron transport chain were deficient. Scherzer believes mitochondrial activity may be affected by a combination of environmental chemicals, risk genes, and aging. “The combination may lead to the pervasive electron transport chain deficit we found in common Parkinson’s disease and to which dopamine neurons might be intrinsically more susceptible.”

Works Cited:

American Association for the Advancement of Science. “In Parkinson’s diseases, brain cells abandon mitochondria.” ScienceDaily. 8 Oct. 2010. Web. 20 July 2011.

Fester, R. (2011). E-z microbiology. NY: Barrons Educational Series Inc.

Shier, David, Jackie Butler, and Ricki Lewis. Hole’s human anatomy & physiology. 12th ed. 2010. Pg. 406. Print.

"Substantia nigra and Parkinson's disease." Medline Plus. Web. 22 Jul 2011.

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