Decades ago, Braak hypothesized that α-syn proteins associated with Parkinson's disease might travel up the nerves connecting the gut to the brain as if they were climbing a ladder. As you can see in the illustration above from Dawson's latest study (2019) in mice, Braak's theory might be right.
Advanced Parkinson's disease is characterized by impaired movement and cognitive deficits along with α-synuclein buildup in the brain. As more of these neuron-damaging proteins clump together, it creates a snowball effect that kills brain cells. This dead brain matter is called "Lewy bodies."
Notably, according to another senior co-author, Han Seok Ko, the initial appearance of toxic α-syn proteins in the gut is consistent with one of the earliest symptoms of Parkinson's, which is constipation. Ko is an associate professor of neurology at the Johns Hopkins University School of Medicine.
Through a series of elaborate experiments in mice, Dawson and colleagues were able to show that pathologic α-synuclein can be transmitted up to the brain via the vagus nerve. According to the researchers, severing or blocking vagal transmission pathways with a "vagotomy" might be a way to halt or prevent some of the physical and cognitive manifestations associated with progressive Parkinson's disease.
The next phase of research by the Johns Hopkins team is to pinpoint precisely what parts of the "wandering" vagus nerve are hijacked as toxic α-synuclein proteins climb from the gut to the brain and to identify the best way to stop this transmission.
Note: Another potentially groundbreaking Parkinson's disease study from earlier this month (Wilson et al., 2019) by researchers at King's College London reported that a loss in serotonin function might be an early warning sign of the condition. (See, "Serotonin Malfunctions May Be a Harbinger of Parkinson'
Sangjune Kim & Seung-Hwan Kwon, Tae-In Kam, Nikhil Panicker, Senthilkumar S. Karuppagounder, Saebom Lee, Jun Hee Lee, Wonjoong Richard Kim, Minjee Kook, Catherine A. Fos, Chentian Shen, Hojae Lee, Subhash Kulkarni, Pankaj J. Pasricha, Gabsang Lee, Martin G. Pomper, Valina L. Dawson, Ted M. Dawson & Han Seok Ko. "Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease." Neuron (First published: June 26, 2019) DOI: 10.1016/j.neuron.2019.05.035
Heather Wilson, George Dervenoulas, Gennaro Pagano, Christos Koros, Tayyabah Yousaf, Marina Picillo, Sotirios Polychronis, Athina Simitsi, Beniamino Giordano, Zachary Chappell, Benjamin Corcoran, Maria Stamelou, Roger N. Gunn, Maria Teresa Pellecchia, Eugenii A Rabiner, Paolo Barone, Leonidas Stefanis, and Marios Politis. "Serotonergic Pathology Linked with the Premotor Phase of A53T α-Synuclein Parkinsonism and with Disease Burden: Cross-Sectional Studies” The Lancet Neurology (First published: June 19, 2019) DOI: 10.1016/S1474-4422(19)30140-1
Retrieved from PsychologyToday on June. 27, 2019. Christopher Bergland. "Parkinson's Disease-Causing Protein Hijacks Gut-Brain Axis"