Identification of new Parkinson's genes playing a role in mitochondrial quality control

Currently, there are no disease-modifying treatments that can prevent or slow down PD.

PD, like other neurodegenerative conditions, is a disorder involving both genetic (e.g. _PINK1_ and _Parkin_ genes) and environmental factors (e.g. age, pesticides). Recently, multiple regions of PD patient's DNA were found to be different to those not having the disease, suggesting these differences may be involved in increasing the chances of developing PD. However, these DNA regions contain multiple genes, therefore we must specifically determine which gene(s) is responsible for increased disease risk so that we can ascertain why and how PD develops, thus allowing us to develop new therapies.

From previous studies we know that a significant number of PD genes play a role in the maintenance of mitochondria health, thus various genetic changes can lead to mitochondrial dysfunction, causing cell death leading to PD. Mitochondria are important to the cell, especially in brain cells (called neurons) as they are the "power stations" of the cell, producing energy that is required for them to function and survive. Cells have developed a sophisticated mechanism to remove these dysfunctional mitochondria from the cell so that they do not cause cell death. This process is termed mitophagy. This is orchestrated by _PINK1_ and _Parkin_, however, this only happens in some PD patients, therefore there is likely to be several other genes that contribute to PD risk.

The HPF lab, in collaboration with the AR-UK UCL DDI, has developed techniques to identify which genes play a role in mitophagy. In collaboration with GSK, we will generate iPSC dopaminergic neurons (cells that die in PD) and utilise advanced genetic screening techniques to determine which of these PD risk genes regulate mitophagy. The unique convergence of expertise will allow a powerful multidisciplinary approach to accelerate a deep understanding of the role of mitophagy in PD driving forward the design of novel treatments for PD.