Research shows that problems with recycling in brain cells in Parkinson's are overcome by the malaria drug clioquinol.
Scientists at the Oxford Parkinson's Disease Centre have uncovered a potential way that a malaria drug could protect brain cells in people with Parkinson's. The early stage research, published in the journal of Human Molecular Genetics, found that the drug could resolve the problems with recycling that are seen in a rat model of Parkinson's.
A recycling problem
It's essential that our brain cells are kept healthy and free of waste in order for them to function properly. One way cells are kept 'clean' is through their very own recycling system, made up of structures called lysosomes. These are acidic sacks filled with digestive enzymes capable of breaking down waste material within the cell. When the recycling process is not working efficiently, waste can quickly build up. This can alter the cells' behaviour and ultimately lead to the cell death.
Changes in the LRRK2 gene are linked to an increased risk of developing Parkinson's. This gene holds the instructions for the LRRK2 enzyme that controls many processes within the cell, including recycling. Parkinson's-associated changes in the LRRK2 gene is thought to cause a problem with the recycling system, leading to unwanted proteins building up inside brain cells.
Dr Katherine Fletcher, Research Communications Officer at Parkinson's UK, said:
"We know that in people living with Parkinson's, there is a problem with recycling in brain cells that can stop them from functioning properly - but there is a lot we don't understand. This early stage research uncovers more clues about what is going wrong in Parkinson's brain cells and identifies an exciting new drug target.
"Understanding more about Parkinson's is vital in the search for treatments that can slow or stop the progression of Parkinson's, which is desperately needed for the 145,000 people in the UK affected by the condition."
A new drug target
The new study found that rats containing a LRRK2 mutation had decreased levels of recycling in brain cells, due to the lysosomes becoming less acidic. However, the malaria drug clioquinol was shown to increase the acidity of the lysosomes back to normal levels, and this restored effective recycling in the cells.
These new results uncover a novel role for LRRK2 in regulating the acidity of the lysosome, as well as reaffirming the potential of targeting the recycling system in brain cells for therapeutic use.