Study Rationale:
Accumulation of damage to the cellular batteries (mitochondria) in the brain is a major driver of PD. Analysis of two genes PINK1 and PARKIN have provided clues about how brain cells clear damaged mitochondria. However current understanding of this pathway is still rudimentary and does not explain variation amongst patients in terms of symptom onset and progression. We will build on exciting new findings which point to stress pathways both within and outside the mitochondria that play an important role in how brain cells respond and clear damaged mitochondria and influence disease in people with PD.
Hypothesis:
Our working hypothesis is that impaired mitochondrial clearance is a major driver of PD and we aim to define the new understanding of how stress pathways acting both inside and outside mitochondria, impact mitochondrial clearance pathways in order to discover new treatments.
Study Design:
We will use cutting edge technologies including a powerful microscope known as cryo-electron tomography that enables visualization of changes in cells at the atomic level and new methods to rapidly isolate mitochondria and study what is wrong by sequencing the proteins within them. These and other techniques will be applied to different types of Parkinson’s models including brain cells in a dish and animal models which are engineered to express genes linked to Parkinson’s. We will test and evaluate whether our discoveries really matter to the disease by analysing human brain tissue from people with Parkinson’s.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Our work will uncover fundamental new mechanisms and cellular pathways that may lead to new ideas for diagnosis and treatment of Parkinson’s.
Next Steps for Development:
We will share our discoveries with the whole community to enable our findings to be tested and validated in different types of samples of Parkinson’s and this will be important in leveraging support from drug companies to initiate drug development programmes based on our work.