Environmental Risk Factors For Parkinson'S Disease

In 1983, Langston and co-workers discovered that intravenous injection of the toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) from failed drug synthesis was able to induce parkinsonian syndrome (Langston et al. , 1983; Zeng et al. , 2018). Since then, epidemiological research has revealed several environmental and lifestyle-linked factors that are key elements underlying the pathogenesis of idiopathic PD and contribute to genetic predisposition (Tanner, 1989, 2010; Tysnes and Storstein, 2017).

This evidence is in concordance with the fact that more than 90% of PD cases do not have a clear genetic cause and some risk factors can be modulated in experimental models of the disease, promoting a neuroprotective or neurotoxic effect (Ascherio and Schwarzschild, 2016a). Some people are exposed to environmental toxins during their lives that, together with genetic predisposition, would cause PD. In the beginning, these sporadic cases manifest no clinical signs, even though the disease has already developed, and neurodegeneration is progressing (Fereshtehnejad et al. , 2017). Aging is an important contributing factor that accelerates the neurodegenerative process to reach the clinical threshold to be detected (Rodriguez et al. , 2015; Fereshtehnejad et al. , 2017). In this sense, early markers of the disease are needed to be able to start treating even when clinical features are not manifested. Excluding those PD cases that develop <45 years old, who have a strong genetic component, advanced age is considered the main risk factor that contributes to PD (Collier et al. , 2017). Several epidemiologic studies have made clear that as age increases, so does PD prevalence (Collier et al. , 2017). It is also known that age of onset also determines phenotype and evolution of the disease as early-onset and late-onset cases show significantly different clinical pictures (Rodriguez et al. , 2015; Collier et al. , 2017).

Also, extensive evidence shows that the progressive decline that characterizes aging is strongly associated with many PD pathological markers as mitochondrial impairment, increased oxidative stress or protein homeostasis dysregulation (Kaushik and Cuervo, 2015; Rodriguez et al. , 2015; Rango and Bresolin, 2018). Additionally, the aging process may also affect the SNpc DA neurons vulnerability to degenerate in PD (Rodriguez et al. , 2015; Surmeier et al. , 2017). Other circumstances that have been demonstrated to be capable to increase PD risk are high consumption of dairy products (Sääksjärvi et al. , 2013; Ascherio and Schwarzschild, 2016b), exposure to pesticides and other environmental chemicals (Petrovitch et al. , 2002; Kamel et al. , 2007; Ascherio and Schwarzschild, 2016b), use of amphetamine and methamphetamine (Callaghan et al. , 2010; Ascherio and Schwarzschild, 2016b), suffering from melanoma (Wirdefeldt et al. , 2014) and traumatic brain injury (Gardner et al. , 2015). Controversial results have been found in the link between high PD risk and body-mass index, diabetes, blood cholesterol, reproductive hormones or vitamins and other micronutrients (Ascherio and Schwarzschild, 2016b).