A new study published recently in eLife has demonstrated the removal of damaged mitochondria from the brain cells of mice treated with a small molecule compound for Parkinson’s disease-causing mutation.
Parkinson's. Image Credit: Kotcha K/Shutterstock.com
The study results could help elucidate how dopamine-producing brain cells are affected in people with mutations that cause Parkinson’s disease.
The progressive loss of brain cells that synthesize dopamine causes Parkinson’s disease. This results in the characteristic symptoms of the disease, such as sleep problems, tremors, dementia, and rigid movements.
Scientists believe the death of these cells in people with Parkinson’s disease is caused, in part, by the failure of a quality control mechanism that removes damaged energy-producing structures in the cells called mitochondria. This failure to recycle damaged mitochondria is detrimental to the health of brain cells.”
Francois Singh, Study First Author and Postdoctoral Research Assistant, Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
Singh and his team wished to study this in-depth and hence collaborated with researchers from the Division of Signal Transduction Therapy, a consortium of academia and pharmaceutical companies.
Jointly, they employed the most advanced technologies to observe the recycling of mitochondria in the brains of mice with the most common Parkinson’s disease-causing mutation in a gene named LRRK2.
The experiments revealed that damaged mitochondria are not eliminated effectively in the dopamine-producing brain cells of the animals and that damaged components in other kinds of brain cells are recycled. This could account for the selective loss of dopamine-producing brain cells in Parkinson’s disease and the association of all symptoms with a lack of dopamine.
The LRRK2 gene mutation leads to the production of a hyperactive version of the protein. Therefore, a small molecule that suppresses the hyperactive protein was used to treat the mice and it was found that the mitochondria recycling was restored in the dopamine-producing brain cells of the animals.
According to the researchers, the findings of the study constitute a crucial step forward in the pursuit to comprehend mechanisms underlying this disease, which is incurable at present. The findings should help induce and focus studies in this area.
Not only have we discovered new biology, but we have also shown that an LRRK2 inhibitor can rescue a mitochondrial defect related to Parkinson’s disease. These findings highlight the significant benefit of academic-industrial collaborations that will hopefully accelerate the development of new treatments for Parkinson’s disease.”
Ian Ganley, Study Senior Author, MRC Investigator and Scientific Programme Leader, Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
Singh, F., et al. (2021) Pharmacological rescue of impaired mitophagy in Parkinson’s disease-related LRRK2 G2019S knock-in mice. eLife. doi.org/10.7554/eLife.67604.