Researchers at the University of Rochester Medical Center have put forth a new hypothesis suggesting that toxic substances entering the body via the nose or gut may give rise to toxic protein clumps that eventually cause Parkinson's disease. The study, titled "The Body, the Brain, the Environment, and Parkinson's Disease," was published in the Journal of Parkinson's Disease.

Dr. Ray Dorsey, a professor at the University of Rochester Medical Center, stated that in both the "brain-first" and "body-first" scenarios, the disease mechanism arises in structures in the body closely connected to the outside world. This reinforces the idea that Parkinson's, which is currently the world's fastest-growing brain disease, may largely be preventable if the sources of toxicants are identified and avoided.

Toxicants, such as pesticides, dry cleaning chemicals, and air pollutants, are believed to play a role in the development of Parkinson's disease. Farmers exposed to the pesticide paraquat have a higher risk of developing the disease and progressing more rapidly. Industrial chemicals like trichloroethylene (TCE) and particulate matter suspended in polluted air have also been suggested as potential causes.

The debate over the origin of Lewy bodies, the protein clumps that are toxic to nerve cells in Parkinson's disease, centers around whether they first form in the brain or the gut. Both the nose and gut have well-established connections to the brain. In the "brain-first" hypothesis, chemicals are inhaled through the nose and rapidly travel to the brain, potentially leading to faster disease progression. In the "body-first" hypothesis, the chemicals are ingested and pass through the lining of the gut where Lewy bodies begin to form. They then spread to the brainstem and other body parts through the vagus nerve.

A hypothesis proposed by Dr. Dorsey and researchers in the United States and Denmark combines both the "brain-first" and "body-first" scenarios. They suggest that toxic substances entering the body via different routes could lead to different forms of the disease. The researchers write that Parkinson's is a systemic disease and that its initial roots likely begin in the nose and gut, tied to environmental factors increasingly recognized as major contributors to the disease.

The timing, dose, and duration of exposure, as well as interactions with genetic and other environmental factors, are considered key factors in determining who ultimately develops Parkinson's disease. It is believed that these exposures likely occurred years or even decades before symptoms develop.

The hypothesis aligns with the observation that regions with reduced use of harmful chemicals, improved air quality, and banned pesticides may see a decrease in the occurrence of Parkinson's disease over time. Conversely, regions with increased exposure to toxic substances, such as sub-Saharan Africa where pesticide use has tripled in the past 30 years, may witness a rise in cases.

Further research is needed to understand the role of the skin, the influence of the microbiome, and the effects of ongoing exposures in Parkinson's disease. Animal models could prove useful in studying the interaction between genetic and environmental factors and developing prevention strategies, as well as improving diagnosis and treatment options.

The proposed hypotheses shed light on the complex relationship between the body, the brain, and environmental factors in the development of Parkinson's disease. While many questions remain unanswered, this research opens the door to potential prevention strategies and a deeper understanding of the disease.