A new perspective on parkinson's disease: pathology begins in the gastrointestinal tract

Abstract

2016). Alpha-synuclein aggregation leads to Lewy body formation, the characteristic pathological marker. It is currently unclear whether dopaminergic atrophy leads to alpha-synuclein aggregation or if it is the aggregates that lead to cell death. Few causative factors have thus far been supported, though some environmental toxins have been shown to cause disease symptomology (Pan-Montojo & Reichmann, 2014). For example, exposure to the herbicide Paraquat can result in dopaminergic degeneration and Lewy body formation in the substantia nigra by generating high levels of oxidative stress (Pan-Montojo & Reichmann, 2014). In addition, the production of the synthetic opioid drug MPPP can generate an accidental compound MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), which quickly induces a Parkinsonian state when its toxic metabolite inhibits complex I of the electron transport chain (Pan-Montojo & Reichmann, 2014). The possibility of an endogenous neurotoxic mechanism that was acquired in early life has been contemplated for many years (Gibb & Lees, 1988). It is thought that this potential pathogen is transported from the gastrointestinal (GI) tract to the brain via the vagus nerve over the course of twenty years (Syensson et al., 2015). Svensson and colleagues (2015) examined a cohort of patients who underwent vagotomies. They found that patients who received a truncal vagotomy (i.e., the surgical severance of both vagal trunks) had a lower risk of Parkinson’s disease compared to a INTRODUCTION Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder in the elderly population, following Alzheimer’s disease (Lin et al., 2014). PD is a chronic disorder, characterized primarily by motor deficits including resting tremor, rigidity, bradykinesia, and postural instability (Burke & O’Malley, 2013; Choi et al., 2016; Lohr & Miller, 2014; Miller et al., 1999; Taylor et al., 2014). Although dopaminergic atrophy in the substantia nigra pars compacta mediates the presence of these motor deficits, the clinical indicators do not appear until over 70% of dopamine (DA) nerve terminals in the striatum have atrophied, suggesting the presence of compensatory mechanisms (Bezard et al., 2013). In disease propagation, alpha-synuclein proteins bind ubiquitin ligands and accumulate in damaged cells (Rao & Gershon, A New Perspective on Parkinson’s Disease: Pathology Begins in the Gastrointestinal Tract