Abstract: Parkinson's disease (PD) is the fastest growing neurodegenerative disease in the world and there is still no cure. People with PD experience a variety of motor symptoms due to the death of dopaminergic neurons in the brain, but also non-motor symptoms including gastrointestinal discomfort. Research has indicated that the microbiota-gut-brain axis might play an important role in PD especially considering that the gastrointestinal problems may begin as many as 10 years before the onset of motor symptoms. My research has two focuses: how can we improve the study of the microbiota-gut-brain axis in preclinical models to gain a better understanding? And can these microbiota-gut-brain interactions be a new therapeutic target in PD? To answer the latter question we evaluated an inhibitor of the toll-like receptor 4 (TLR4) in an in vivo model of PD. Activation of TLR4, by for example bacteria of the microbiota, results in inflammation. This inflammation has been shown to drive neurodegeneration in PD. Furthermore previous research from our own research group has shown a genetic knockout to be protective for developing PD in the same in vivo model. We saw that indeed TLR4 inhibition provided a viable therapeutic option with improved motor symptoms, less dopaminergic neuron death, and importantly an improvement in gastrointestinal symptoms. This would suggest that inhibition of TLR4 and, to a wider extent, targeting the microbiota-gut-brain axis could provide a new therapeutic approach in PD.