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As is the case for many neurodegenerative conditions, Parkinson's disease is associated with the spread of protein aggregation. Specific proteins become changed in ways that cause them to form solid deposits, surrounded by a halo of associated toxic biochemistry that harms neurons. The aggregates in Parkinson's patients are formed from α-synuclein, and here, researchers provide evidence for the origins of α-synuclein related neurological dysfunction to begin in the intestine, and only later migrate to the brain.

Parkinson's disease is characterised by a slow destruction of the brain due to the accumulation of the protein alpha-synuclein and the subsequent damage to nerve cells. The disease leads to shaking, muscle stiffness, and characteristic slow movements of sufferers. In a new research project, scientists used genetically modified laboratory rats which overexpress large amounts of the alpha-synuclein protein. These rats have an increased propensity to accumulate harmful varieties of alpha-synuclein protein and to develop symptoms similar to those seen in Parkinson's patients. The researchers initiated the disease process by injecting alpha-synuclein into the small intestines of the rats.

"After two months, we saw that the alpha-synuclein had travelled to the brain via the peripheral nerves with involvement of precisely those structures known to be affected in connection with Parkinson's disease in humans. After four months, the magnitude of the pathology was even greater. It was actually pretty striking to see how quickly it happened."

Patients with Parkinson's disease often already have significant damage to their nervous system at the time of diagnosis, but it is actually possible to detect pathological alpha-synuclein in the gut up to twenty years before diagnosis. "With this new study, we've uncovered exactly how the disease is likely to spread from the intestines of people. We probably cannot develop effective medical treatments that halt the disease without knowing where it starts and how it spreads - so this is an important step in our research. Parkinson's is a complex disease that we're still trying to understand. However, with this study and a similar study that has recently arrived at the same result using mice, the suspicion that the disease begins in the gut of some patients has gained considerable support."

Link: https://www.eurekalert.org/pub_releases/2019-09/au-pdm090219.php