Impact of environmental toxicants exposure on gut-brain axis in Parkinson disease.

Abstract

Parkinson disease (PD) is a major public health challenge as many of the current drugs used in its management provide symptomatic relieve without preventing the underlying cause of the neurodegeneration. Similarly, the non-motor complications of PD, especially the gastrointestinal tract (GIT) disturbance increases the disease burden on both the PD patient and caregivers. Different theories have been postulated regarding the mechanisms or pathways involved in PD pathology but gut-brain axis involvement has gained much more momentum. This pathway was first suggested by Braak and colleagues in 2003, where they suggested that PD starts from the GIT before spreading to the brain. However, human exposure to environmental toxicants known to inhibit mitochondrial complex I activity such as rotenone, paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are well associated with PD. Several reports have shown that oral exposure of laboratory animals to rotenone causes mitochondria dysfunction, GIT disturbance, overexpression of alpha synuclein and microbiota imbalance. This review focuses on the mechanism(s) through which rotenone induces PD pathogenesis and potential for therapeutic small molecules targeting these processes at the earliest stages of the disease. We also focused on the interaction between the GI microbiota and PD pathology.