Parkinson's Disease and Neurodegeneration group
Parkinson’s disease is a chronic, debilitating neurodegenerative disorder that currently afflicts more than five million people globally. This figure is predicted to increase by 50% in the next 20 years, as our population ages.
Although it is predominantly considered a movement disorder, people with Parkinson’s disease also experience significant non-motor symptoms including sleep disturbances, olfactory dysfunction, autonomic dysfunction and changes in cognition. There is no cure for Parkinson’s disease and current therapies are only partially effective at treating some symptoms while progression and spread of the disease continues, making the need for new treatments critical.
The lack of knowledge of the underlying mechanisms responsible for causing Parkinson’s disease and its progression is the major impediment to therapeutic advances and a cure. To achieve earlier diagnoses and development of treatments, our research focuses on discovering the cascade of molecular and cellular events that cause the loss of neurons in Parkinson’s disease. To accomplish this, we are taking a multifaceted approach involving the following:
1. Neurogenomics: Specific regions of the human genome are significantly associated with Parkinson’s disease, only some of which are protein-coding genes. To understand how these regions might contribute to the disease, we are identifying which RNA transcripts are encoded at these regions. This approach is ongoing but we have already discovered a family of long non-coding RNAs (lncRNAs) that appear to be intimately involved in Parkinson’s disease, potentially in a causative role. lncRNAs have been found to be involved in multiple regulatory pathways such as alternative splicing, transcriptional, post-transcriptional and epigenetic processes, and represent an exciting and previously undiscovered class of factors contributing to neurodegenerative disease. The lncRNAs we have discovered are currently under assessment for both the mechanistic insights they provide into Parkinson’s disease, as well as their use as critically needed Parkinson’s disease biomarkers.
2. Human-induced pluripotent stem cells (hiPS cells): Derived from patients’ fibroblasts and then differentiated into neurons, these cells can recapitulate the disease phenotype(s) and provide access to clinically-relevant cell models. We are using the potential of these cells to validate and extend our findings, especially with respect to the Parkinson’s disease-associated primate specific lncRNAs we have discovered.
3. αSynuclein: This synaptic protein is central to Parkinson’s disease. Its increased expression or mutation results in early onset forms of the disease. Our previous studies have identified some of the toxic consequences of this protein and we have subsequently discovered a cellular dysfunction common to Parkinson’s disease that renders cells hypersensitive to αSynuclein, integrating two major aspects of the disease.
4. Preventing Parkinson's disease progression: Recent evidence suggests that the inevitable progression of neurodegeneration in Parkinson’s disease may involve the ‘release’ of toxic forms of αSynuclein that are then taken up by neighbouring neurons, where they trigger dysfunction. We have identified a gene that contributes to this ‘intraneural transmission’ and are assessing how modulating the expression of this gene impacts disease progression.