Parkinson’s Disease is a neurodegenerative disorder caused by destruction of dopamine-producing cells in the substantia nigra in the midbrain. The exact causes of this cell death are unclear, and several hypotheses have been tested and rejected time and time again (e.g., the autoimmune hypothesis). Parkinson’s Disease is part of a class of neurodegenerative diseases called ‘synucleinopathies’, which are characterized by aberrant aggregations of a protein called alpha-synuclein. Aggregates of this protein can be viewed in brain sections (using a microscope) and are termed ‘Lewy Bodies’. They spread throughout the brain in a characteristic pattern during the course of Parkinson’s disease, typically starting in the dorsal motor nucleus of the vagus (DMV) before reaching the midbrain. This suggests that problems may begin in downstream areas that relay signals through the DMV…like the gut. Whether alpha-synclein can travel from the gut to the brain has been a challenging question to answer. Using a clever approach, Ko & colleagues demonstrated that this is indeed possible when the protein is artificially induced into the stomach/small intestine area (see the figure below). A thing to keep in mind, however, is that this paper demonstrates that such a mechanism can exist, it doesn’t provide evidence that it does exist or ‘causes’ Parkinson’s disease in humans.

To cut a very long story short, others have shown that a pathogenic variant of alpha-synuclein can be made in a dish (in vitro), where they are termed ‘pre-formed fibrils; PFFs’. These fibrils can ‘jump’ from neuron-to-neuron in a living organism (in vivo) and cause symptoms remarkably similar to those found in sporadic Parkinson’s disease. The authors took advantage of these PFFs to test their hypothesis by injecting them into various parts of the gastrointestinal system, and seeing if they would ‘jump’ along nerve cells up to the brain, where they could promote the development of Parkinson’s disease.