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Parkinson’s disease (PD) is the most common cause of parkinsonism and neurodegenerative disorder after Alzheimer’s disease. It is caused by the progressive loss of dopaminergic neurons of the substantia nigra pars compacta which is accompanied by the presence of Lewy bodies. Its diagnosis is clinical and there is a risk of misdiagnosis with other causes of parkinsonism. PD is exceptional before age 50, and its frequency increases with age, with an incidence of about 1 to 5 per 1000 person-years after age 60. PD has consistently been shown to be about 1.5 times more common in men than in women. PD is considered as a multifactorial disease resulting in the majority of cases of multiple factors. Monogenic PD occurs in a minority of patients, but several small-effects susceptibility genes are implicated in sporadic forms. Heritability is however small, and it is generally considered that environmental factors are involved in PD aetiology.
The hypothesis of a link between PD and pesticide exposure appeared in the early 1980s’, after several cases of parkinsonism occurred following intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP can cross the blood–brain barrier and is metabolised in glial cells by enzyme monoamine oxidase B into 1-methyl-4-phenylpyridinium (MPP+), a substrate of the dopamine transporter that inhibits the complex I of the mitochondrial electron transport chain and leads to the degeneration of nigral dopaminergic neurons. MPTP-induced animal models represent one of the main tools for investigations into the mechanisms involved in the death of dopaminergic neurons in PD.1 This molecule has a chemical structure similar to that of paraquat, a non-selective herbicide marketed since the 1960s and widely used since. Following this accidental observation, numerous epidemiological studies have examined the relationship of farming and pesticides exposure with PD, and toxicological studies have investigated some of the mechanisms involved for specific …
Footnotes
Contributors AE and FM were responsible for writing the editorial.
Funding AE receives funding from the French National Research Agency (ANR) and Joint Programme—Neurodegenerative Disease Research (JPND), Agence nationale de sécurité du médicament et des produits de santé (ANSM), and Institut de recherche en Santé Publique (IReSP).
Competing interests None declared.
Provenance and peer review Commissioned; externally peer reviewed.