Scientists say they have discovered that a chemical used in anti-wrinkle cream has potential to prevent early-onset Parkinson’s disease.
The findings could be used to develop drugs to prevent the cell death seen in the brains of people with Parkinson’s disease, say the researchers from the University of California in San Francisco (UCSF).
The study, published in the journal Cell, analyzes the use of kinetin triphosphate (KTP) – a plant hormone that promotes cell division – as a way of increasing mutant PINK1 enzyme activity in the nerve cells to levels that are nearly normal.
According to the researchers, mutated PINK1 enzymes are directly responsible for many early-onset cases of Parkinson’s disease.
Once PINK1 enzymes are mutated, this causes harm to the mitochondria – parts of the cells that are responsible for the conversion of food energy into alternative forms of energy used by cells.
When the performance of mitochondria is harmed, this can cause the death of nerve cells that produce dopamine within a brain region called the substantia nigra. This area of the brain controls movement, and lack of dopamine in this region is a cause of tremors, a common symptom of Parkinson’s disease.
Dr. Kevan Shokat, a chemist at UCSF, says:
“In light of the fact that mutations in PINK1 produce Parkinson’s disease in humans, the finding that kinetin can speed mutated PINK1 activity to near normal levels raises the possibility that kinetin may be used to treat these patients.”
The researchers also discovered that when nerve cells with non-mutated PINK1 interacted with kinetin, enzyme activity also sped up ahead of normal levels.
The study authors say these findings may be relevant for the most common forms of Parkinson’s disease, where PINK1 is not mutated.
A previous study revealed that when PINK1 showed similar overactivity in a fruit-fly model, the abnormal movement of Parkinson’s disease caused by another defect slowed down. In this case, the defect was increased production of alpha-synuclein – a cause of some inherited types of Parkinson’s disease.
For this most recent study, Dr. Shokat decided to target the substrate of PINK1 called ATP – a molecule that binds to the enzyme and triggers a fast chemical transformation. This chemical reaction encourages the activation of the Parkin enzyme.
The authors describe how both the PINK1 and Parkin enzymes work together to monitor the health of mitochondria, helping to trigger the repair or disposal of damaged mitochondria within the cells, encouraging cell survival.
Dr. Shokat says that although there have been many drugs developed that inhibit the activity of kinases, none has yet been marketed that directly boosts the activity of kinase.
“Therapeutic approaches for enhancing the activity of PINK1 had not been considered, because scientists had not conceived of the idea of developing a new substrate for the enzyme.”
“We found that a small molecule, called KTP, speeds chemical reactions catalyzed by PINK1 better than ATP, the natural substrate. That kind of better-than-natural response is essentially unheard of.”
The researchers add that these findings may prompt the development of similar pharmaceutical treatments that could be used to tackle other diseases, such as cancer and diabetes.