Promising Outcomes of Original Grant:
Parkinson's disease involves toxic forms of certain proteins (e.g., alpha-synuclein) in the brain, which trigger an immune response driven by inflammatory lymphocytes. These lymphocytes can contribute to the death of brain cells and progression of Parkinson's. Previous findings indicate that pre-clinical models deficient in lymphocytes do not develop Parkinson's disease. Our recent results demonstrated that a receptor for dopamine (DR), a substance produced by the nervous system, plays a pivotal role in the death of brain cells caused by lymphocytes. Inhibiting the dopamine receptor slowed the development of Parkinson's disease in a pre-clinical model.
Objectives for Supplemental Investigation:
Our hypothesis is that inhibiting the dopamine receptor weakens immune response driven by inflammatory lymphocytes, which in turn reduces brain cells death. We will further test this in pre-clinical models with pathogenic proteins in the brain, to determine if inhibiting the dopamine receptor in this more complex system still provides a therapeutic benefit. Our goal is to understand how inhibition of the dopamine receptor affects the behavior of inflammatory lymphocytes, their infiltration in the brain and subsequent brain cell death.
Importance of This Research for the Development of a New PD Therapy:
This research will allow us to confirm the therapeutic potential of dopamine receptor inhibitors in another model of Parkinson's disease, a step necessary to include in preclinical studies before we could advance to human clinical studies. Moreover, this research will give us a deeper insight of the biological mechanism underlying the therapeutic effect of inhibiting dopamine receptors. The results of this study could increase our knowledge of Parkinson's disease, allowing us to develop new therapeutic strategies.