Age is the primary risk factor for the development of a neurodegenerative disease such as Parkinson’s disease with projected disease burden expected to increase 2-fold in Ireland by 2036. The overall burden is likely to keep increasing unless mechanistic based strategies for alleviating this age related neural decline are discovered and exploited for prevention or therapy. The potential role of the astrocytes as either a cellular target or as a secondary participant in the pathogenesis of neurodegenerative disease has gained attention in recent years as has the role of the immune system. However, our understanding of astrocytic mechanisms in response to stress/injury is incomplete compared to that of neurons and our understanding of the role the immune system plays is still in its infancy.
The aim of this project is to determine the interplay between T cells (specifically Th17 cells) and astrocytes and how either cell type alone or following stimulation of the astrocytes with microglial secreted factors affects the survival of midbrain dopamine neurons. We will generate midbrain dopamine neurons and midbrain astrocytes from a number of induced pluripotent stem cell lines, including idiopathic Parkinson’s and normal controls and we will isolate Th17 lymphocytes from whole blood of Parkinson’s patients and controls.
In addition, we will utilise Mass Spectroscopy to determine what factors are secreted by astrocytes. Specifically we will collect astrocyte conditioned media before and after their exposure to Th17 cells or microglial secreted factors and determine what factors are detrimental to dopamine neuronal survival. This body of work will determine how the interplay of the immune system with cells of the brain is implicated in the pathogenesis of Parkinson’s disease.