New hypothesis implicates environmental chemicals in Parkinson’s cause

A new theory has been proposed for the cause of Parkinson’s disease, which affects millions of people worldwide and its growth sees no signs of slowing down.

Parkinson’s disease (PD) is a progressive neurodegenerative disease estimated to effect more than 8.5 million individuals in 2019 though the exact causes remain uncertain.

Symptoms of PD include motor symptoms – such as tremor, involuntary movement, imbalance, and rigidity – and non-motor symptoms such as cognitive impairment, mental health and sleep disorders, and dementia.

Recent theories around the causes suggest the disease is the result of processes that start in either the brain’s olfactory system (brain-first) or the body’s intestinal tract (body-first).

Now a new idea – which has yet to be tested – proposes environmental exposure to toxicants may cause either body-first or brain-first PD.

The article outlining the theory has been printed as an ‘hypothesis paper’ in the Journal of Parkinson’s Disease, to coincide with World Parkinson Day (April 11). The hypotheses in the paper are based on a review of the available scientific evidence and have not been tested yet.

“In both the brain-first and body-first scenarios the pathology arises in structures in the body closely connected to the outside world,” says Ray Dorsey, a professor of neurology at the University of Rochester Medical Center in the US and co-author of the paper.

“Here we propose that Parkinson’s is a systemic disease and that its initial roots likely begin in the nose and in the gut and are tied to environmental factors increasingly recognised as major contributors, if not causes, of the disease.

“This further reinforces the idea that Parkinson’s, the world’s fastest growing brain disease, may be fuelled by toxicants and is therefore largely preventable.”  

Inside the brains of people with PD, a misfolded protein called alpha-synuclein accumulates in clumps called Lewy bodies. These cause progressive dysfunction and death of many types of nerve cells, including ones in the dopamine-producing regions of the brain that control motor function. 

Dorsey and collaborators reviewed the evidence and suggests the industrial chemicals trichloroethylene (TCE) and perchloroethylene (PCE), the herbicide paraquat, and air pollution, could be common causes for the formation of toxic alpha-synuclein. 

They propose the toxicants’ different routes of entry into the body result in different forms of the disease.

In the brain-first model, they propose chemicals are inhaled through the nose and enter the brain via olfactory nerves. From the brain’s olfactory bulb the alpha-synuclein spreads to other areas, principally on one side of the brain.

In the body-first model they propose chemicals are ingested and pass through the lining of the gastrointestinal tract where they may enter the brain via the vagus nerve. In this sub-type of PD alpha-synuclein can spread to both sides of the brain and spinal cord.

“These environmental toxicants are widespread and not everyone has Parkinson’s disease,” says Dorsey.

“The timing, dose, and duration of exposure and interactions with genetic and other environmental factors are probably key to determining who ultimately develops Parkinson’s.

“In most instances, these exposures likely occurred years or decades before symptoms develop.” 

They outline several testable hypotheses to be explored in future research, including investigating whether theprevalence of Lewy body disorders will vary based on the exposure to environmental toxicants in a given region, and whether animal models will demonstrate a body-first pathological spread for ingested toxicants and a brain-first for inhaled ones.

In addition to the effects of ongoing exposures, the authors say the proposed link also leaves many questions unanswered – such as the role of the skin and the influence of the microbiome.

“Despite these limitations,” they write, “the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson’s disease and open the door toward the ultimate goal – prevention.”

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