Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases

Abstract

Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre- and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.

Alzheimer's Disease with Markedly Elevated Arsenic and Other Metals Masquerading as Organic Brain Syndrome and Affective Disorder

“…As also increases Tau phosphorylation and increases transcription of the amyloid protein precursor gene [15,16]. In addition, As alters amyloid precursor protein metabolism or catabolism increasing both APP and sAPPbeta levels and ABeta [1,17].…”

“…A number of studies suggest a role for Al, Pb and As in the eventual development of AD after prenatal or neonatal exposure [1]. Nonetheless, the role of extensive exposure of metals in adulthood has not been established.…”

“…The role of metals in the development of Alzheimer's disease (AD) remains unproven and controversial [1][2][3][4][5]. Several studies have found high levels of aluminum (Al) arsenic (As), lead (Pb) or cadmium (Cd) in the blood, cerebrospinal fluid or brains of patients with cognitive impairment or AD [1][2][3][4][5][6][7][8][9][10][11][12].…”

“…Several studies have found high levels of aluminum (Al) arsenic (As), lead (Pb) or cadmium (Cd) in the blood, cerebrospinal fluid or brains of patients with cognitive impairment or AD [1][2][3][4][5][6][7][8][9][10][11][12]. In experimental studies, adult exposure to several metals have been shown to alter amyloid precursor protein synthesis or catabolism and, in some cases, been correlated with the development of AD pathology [1,2,5,10 ]. Nonetheless, there have been few reports of high levels of several neurotoxic metals in tissues of an unfortunate individual who developed AD.…”

Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease

“…Neuronal dysfunction can be caused by environmental factors, such as exposure to pesticides and neurotoxic metals, or by the inheritance of disease-causing alleles in specific genes (Johnson, 1991;Chin-Chan et al, 2015). Although either environmental or genetic influences can independently lead to these diseases, in many cases a combination of genetic risk factors and toxin exposure determines the disease onset (Kalia and Lang, 2015).…”