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.

Double Trouble: How Microbiome Dysbiosis and Mitochondrial Dysfunction Drive Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

“…The gut microbiota and their metabolites play crucial roles in processes such as mitochondrial biogenesis, metabolism, and modulation of oxidative stress. In recent studies, a strong connection between the microbiota and mitochondria has been extensively elucidated in various diseases [ 50 , 51 , 52 , 53 ]. The mitochondria serve as the energy source for the continuous production of adenosine triphosphate (ATP), and they are also the primary site of cellular reactive oxygen species (ROS) generation.…”

Glutamine metabolism in diseases associated with mitochondrial dysfunction

“…A small group of particularly well documented environmental mitotoxins have been directly linked to human neurodegenerative diseases. These include the ETC complex I (ETC CI) inhibiting pesticide/piscicide rotenone and mitochondrial ROS generating herbicides paraquat and diquat, both linked to Parkinson’s disease through both epidemiologic and pre-clinical studies ( Spivey, 2011 ; Olubodun-Obadun et al, 2022 ; Miyazaki et al, 2020 ; Tanner et al, 2011 ; Tangamornsuksan et al, 2019 ; Drechsel and Patel, 2009 ; Yan et al, 2016 ). The ETC CI inhibiting plant toxin annonacin has similarly been linked to progressive supranuclear palsy (PSP), a disease with similarities to both PD and LS ( Spivey, 2011 ; Olubodun-Obadun et al, 2022 ; Miyazaki et al, 2020 ).…”

Hepatic Mitochondria-Gut Microbiota Interactions in Metabolism-Associated Fatty Liver Disease

“…Mitochondria and gut microbiota closely interact, and a disruption of this interaction is reported in several conditions [ 25 , 26 , 27 , 28 ]. Indeed, intestinal microbiota and related metabolites are determinant for mitochondrial metabolism, biogenesis, and redox homeostasis [ 25 ].…”