The researchers also found that, in nerve cells with normal PINK1, kinetin boosted enzyme activity beyond typical levels. This finding may be relevant for the most common forms of Parkinsons disease, in which PINK1 is not mutated, because a previous study showed that similar overactivity of PINK1 can slow the development of abnormal movement in a fruit-fly model of Parkinsons disease caused by another defect. This defect is elevated production of the protein alpha-synuclein, also a cause of some inherited cases of Parkinsons disease.
The demonstration in the new study that PINK1 can be boosted in human nerve cells that lack PINK1 mutations therefore suggests that kinetin might also have therapeutic potential in common cases of Parkinsons disease in which PINK1 is not mutated, Shokat said.
Parkinsons disease is the second most common neurodegenerative disease after Alzheimers disease, and the 14th leading cause of death in the United States, according to the U.S Centers for Disease Control and Prevention. Current treatments primarily aim to boost availability of dopamine to brain regions where dopamine-producing nerve cells have been lost.
Although many drugs that inhibit the activity of kinases have been developed over the past decade, including 15 currently approved to treat cancer, Shokat said none has yet been marketed to directly boost activity of a kinase.
The breakthrough in revving up PINK1 activity pharmacologically stemmed from Shokats unconventional approach. He targeted the enzymes substrate, a molecule that binds to an enzyme and undergoes a quick ch
|Contact: Jeffrey Norris|
University of California - San Francisco