The characteristic presence of Lewy bodies in the smell-related pathway and in the gut years before the diagnosis of Parkinson’s disease, as well as the potential cumulative impact of different triggers, may help researchers understand the factors environmental factors that contribute to the development of the disease, according to a review study.
The study, “Finding environmental causes of Parkinson’s disease: moving forward», appeared in the Parkinson’s Disease Journal.
Environmental factors contribute at least partially to the late onset of sporadic Parkinson’s disease. Because neurodegenerative changes are too advanced to be stopped or reversed by the time a diagnosis is reached, understanding modifiable risk factors that can help identify the disease and enable early intervention can lead to more effective treatment of the disease. Parkinson’s, the neurological disease with the fastest growing prevalence.
“The main risk factors for [Parkinson’s] are likely environmental and not genetic,” said Honglei Chen, MD, PhD, of Michigan State University, and Beate Ritz, MD, PhD, of the University of California, Los Angeles, in a press release. . “Yet we know relatively little about environmental causes or triggers. Identifying them and defining ways to reduce their impact will be major research challenges for the next two decades.
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Environmental factors can trigger Parkinson’s disease or alter its progression during the prodromal (early) stage, during which early symptoms or signs are present, but clinical diagnosis is not yet possible. Of the factors reported, smoking, coffee, exercise, plasma urate, and ibuprofen use were associated with a lower risk of Parkinson’s disease, while pesticide exposure and brain damage injuries have been associated with a higher risk.
Apart from two pesticides known as rotenone and paraquat, researchers have struggled to provide evidence that other risk factors can cause the disease. Reverse causation – meaning that Parkinson’s disease changes lifestyle and behavior before a clinical diagnosis rather than the other way around – has been offered as an explanation for the link between these environmental triggers and early Parkinson’s disease.
“This prodromal phase is of major interest for prevention efforts,” the researchers said in the statement, adding that the discovery of Lewy bodies – protein aggregates primarily composed of alpha-synuclein characteristic of Lewy disease. Parkinson’s – in the olfactory pathway and digestive tract has made targeting factors that enter the body through the nose or gut “even more important.”
Braak’s hypothesis presents a potential explanation for environmental contributions to the prodromal development of Parkinson’s disease. This suggests that Lewy pathology begins in the olfactory bulb of the brain – an area of the brain involved in smell – or in the enteric (intestinal) nerves (nerve cells that control the function of the gastrointestinal tract) for years or even decades, before reaching the black substance — a key brain area in movement control that shows progressive loss of dopamine-producing neurons in Parkinson’s disease.
Findings such as a decreased sense of smell and constipation years before the diagnosis of Parkinson’s disease supported Braak’s hypothesis. Pesticides and other environmental toxins such as air pollutants, of which there is growing evidence of harmful effects on cognitive function, organic solvents and meats cooked at high temperatures can lead to Parkinson’s disease through these pathways , although a pro-inflammatory gut microbiome—the community of bacteria, viruses, and fungi that live in the gut—has also been proposed as a potential starting point. Certain genetic factors may also interact with these environmental causes to increase the risk of the disease.
Besides Braak’s hypothesis, the scientists also discussed reported epigenetic differences – alterations in gene function but not the DNA sequence itself – in the blood and saliva of people with Parkinson’s disease. , as well as the importance of lifetime exposure to environmental triggers.
The exposome, which refers to all environmental exposures over a lifetime, suggests that several environmental stimuli combine to increase the risk of Parkinson’s disease. This has been shown with traumatic brain injury and paraquat exposure, and with smoking combined with factors such as caffeine intake and physical activity.
“We are at an exciting time to unveil the environmental contributions to [Parkinson’s] development and progression by taking a life-course approach and using new tools to assess environmental exposures,” the researchers said.
Although they caution that the long duration of the prodromal phase complicates understanding of the extent to which environmental factors contribute to Parkinson’s disease, the researchers nevertheless “believe that it will be possible to assess long-term exposures through to large-scale environmental monitoring and using new biomarkers that reflect the exposome.
Braak’s hypothesis and the exposome concept provide “a theoretical framework for scientists to design future studies to decipher the environmental causes of [Parkinson’s] and develop early interventions to arrest progression to characteristic motor dysfunction in [Parkinson’s]“, they concluded.