Funded Studies
Study Rationale: Abnormal accumulation of alpha-synuclein (a neuronal protein) in distinct regions of the brain is a well known feature in Parkinson’s disease (PD). A sizeable number of people with PD exhibit abnormal posture and report pain of uncertain origin. This study aims to investigate the effects of alpha-synuclein accumulation in the neurons of a select brain region, known as the gigantocellular nucleus (GRN) of brainstem, in relation to abnormal posture and pain perception in a preclinical mouse model of PD. We will also analyze the changes in neuronal gene expression, which could suggest a potential disease mechanism.
Hypothesis: We expect that the proposed preclinical model will exhibit abnormal behaviors triggered by the experimentally induced accumulation of alpha-synuclein in the GRN.
Study Design: The study design involves two steps: First, we will surgically deliver abnormal forms of alpha-synuclein, called PFF seeds, into the mouse GRN. We will then study how the accumulation of alpha-synuclein correlates with the appearance of select behaviors (balance and pain perception). Second, we will use advanced methods to assess the subsequent changes in neuronal gene expression patterns and compare these with the changes in gene and protein expression seen in the brains of people with PD.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this study could refine our understanding of the role that alpha-synuclein accumulation in the GRN plays in relation to the development of PD symptoms. In addition, the proposed gene expression studies are expected to guide the discovery of mechanisms relevant to disease.
Next Steps for Development: A positive outcome in these studies will facilitate collaborative efforts with clinical and industry partners to develop novel methods of detecting markers of neuronal dysfunction and potentially disease progression in PD.