Prenatal exposure to oxidative phosphorylation xenobiotics and late-onset Parkinson disease

Abstract

Late-onset Parkinson disease is a multifactorial and multietiological disorder, age being one of the factors implicated. Genetic and/or environmental factors, such as pesticides, can also be involved. Up to 80% of dopaminergic neurons of the substantia nigra are lost before motor features of the disorder begin to appear. In humans, these neurons are only formed a few weeks after fertilization. Therefore, prenatal exposure to pesticides or industrial chemicals during crucial steps of brain development might also alter their proliferation and differentiation. Oxidative phosphorylation is one of the metabolic pathways sensitive to environmental toxicants and it is crucial for neuronal differentiation. Many inhibitors of this biochemical pathway, frequently found as persistent organic pollutants, affect dopaminergic neurogenesis, promote the degeneration of these neurons and increase the risk of suffering late-onset Parkinson disease. Here, we discuss how an early, prenatal, exposure to these oxidative phosphorylation xenobiotics might trigger a late-onset, old age, Parkinson disease.

Keywords: Late-onset Parkinson disease; Mitochondria; Neuronal differentiation; Oxidative phosphorylation; Prenatal exposure; Xenobiotics.