The Effects of Parkinson’s disease Mutations Reversed within Cells

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A recent study from University of California, San Francisco scientists found that a chemical in anti-wrinkle cream could effectively prevent the death of nerve cells that had been damaged by mutations which cause an inherited form of Parkinson’s disease. According to the study’s senior scientist, UCSF chemist Kevan Shokat, PhD; the study targeted an enzyme class known as kinases, and researchers studied how to increase their overall activity. Specifically, the enzyme PINK1 was studied, and in previous studies it has been shown that mutations of the PINK1 enzyme are directly responsible for some cases of early-onset Parkinson’s disease. Within cells in our bodies, the mitochondria is the organelle, or the part of the cell that is the most damaged by loss of PINK1 activity, as the mitochondria is responsible for converting energy from food into usable energy known as ATP. Mitochondria which poorly perform their duties can cause the death of nerve cells within the substantia nigra region of the brain, which plays a major role in controlled movement.. Loss of these cells can lead to tremors and rigidity of limbs that is associated with Parkinson’s disease.

Dr. Shokat’s team of scientists used a chemical called kinetin to increase the level of mutant PINK1 enzyme activity within nerve cells to normal levels of the enzyme’s activity. The researchers found that within nerve cells that had normal levels of PINK1 enzyme activity, kinetin boosted the activity beyond typical levels. A key component of the experiment was Dr. Shokat’s approach; targeting specifically the PINK1 enzyme’s substrate, a molecule that binds to the enzyme, undergoing a chemical transformation. Naturally, PINK1 uses ATP as a substrate, and the overall chemical reaction aids PINK1 to drive the activation of another enzyme, Parkin, which has previously been linked to Parkinson’s disease. PINK1 and Parkin work together to monitor the health of mitochondria within cells, and help to repair or dispose the mitochondria, overall aiding the cell’s survival.

Further studies of the PINK1 enzyme found a new substrate, KTP, which helps PINK1 to speed up catalyzed reactions better than ATP, which was an unexpected find for Shokat’s team. They found that the PINK1 enzyme contains a kind of ‘pocket’ in order to contain the KTP substrate, which is normally too big to fit with other kinase enzymes.

Sources:

1)     Effects of Parkinson’s-disease mutation reversed in cells. (2013, Aug 16th). EurekAlert! Retrieved August 19th, 2013 from http://www.eurekalert.org/pub_releases/2013-08/uoc–eop081613.php

By: Lauren Horne

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