Mitochondrial dysfunction is the root cause of hundreds of diseases, including epilepsy, diabetes and stroke. Because of this link, mitochondrial research has a crucial role in developing treatments for mitochondrial disease and many other conditions. In a recent WCMR Seminar, we heard from PhD student Amelia Lu about her research project that involves investigating the role of mitochondrial changes in Parkinson’s and how this could help guide the development of therapies. Here Amelia tells us more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease. It occurs in ~ 1 in every 100 people over the age of 60. The typical symptoms of PD include resting tremor, rigidity, and gait abnormalities. Mitochondria are the cell’s powerhouse and have their own DNA called mitochondrial DNA (mtDNA), which helps to regulate their function. Mitochondrial dysfunction is linked to a variety of complex diseases, including PD. Deleted mtDNA is detected in post-mortem brain tissue from PD patients, and decreased mitochondria-related protein expression has been seen in two brain regions: the substantia nigra pars compacta (SNpc) and pedunculopontine nucleus (PPN). These are both brain regions that show neuronal loss in PD.
Much of the previous research has been done in the SNpc, with the PPN only coming into the spotlight more recently. The PPN is a complex mid-brain region that consists of three neuron types. Cholinergic neurons are the main population affected in most PD cases. In this research, we will focus on the relationship between mitochondrial DNA changes and cholinergic neuron loss in PD.
To carry out this research, I am going to investigate this in three ways using human postmortem tissue. Firstly, I will look at mtDNA somatic mutations in single neurons as PD neurons tend to accumulate more deletions. I will also investigate how well the neurons are producing proteins critical for the maintenance of both mtDNA and the mitochondria looking at a molecule called mRNA. Lastly, I will look at the actual changes in protein level using immunofluorescence. The outcome of this research will help us understand more about the PPN region, the pathogenesis of PD, and hopefully to guide the development of therapy targeting the PPN region in Parkinson’s.