Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

INTRODUCTION
The finding of MPTP toxicity not only established a link between environmental
exposure and the development of PD, but also introduced MPTP as experimental model
for the study of PD. Other DAergic neurotoxins have been identified, such as the
insecticide rotenone and the herbicide paraquat (Brooks et al. 1999, Betarbet et al. 2000,
Dhillon et al. 2008, Cannon et al. 2009). As MPTP, paraquat and rotenone are selective
complex I inhibitors and induce DA diminution in animal studies. This will be
discussed later in the section “Experimental models of PD”.
Other environmental factors
Since the discovery of MPTP-induced parkinsonism, many epidemiological
studies have been performed to examine the link between the risk of PD and other
environmental factors. Lifestyle-associated factors can have positive or negative
influence on the risk of developing PD. Living in a rural environment (in industrialised
countries), farming, exposure to pesticide use and wood preservatives, and drinking
well water (Hertzman et al. 1990, Engel et al. 2001, Priyadarshi et al. 2001, Baldiet al.
2003, Gorell et al. 2004, Dick 2006) seem to confer an increased risk of PD but it
remains debatable (Koller et al. 1990, Gorell et al. 1998). On the contrary, some
environmental factors appear to exhibit a negative correlation with PD. Caffeine intake,
cigarette smoking, and high vitamin intake are inversely associated with the risk of
developing this disease (Baron 1986, Morens et al. 1995, Ross et al. 2000, Hernan et al.
2002, Lai et al. 2002, Landrigan et al. 2005, de Lau and Breteler 2006).
Metals
Exposure to some specific metals such as aluminium, amalgam, copper, iron,
lead, manganese, mercury, zinc, and a combination of metals have also been
hypothesised to be a risk factor in PD through the accumulation of metals in the SN and
increased oxidative stress (Ngim and Devathasan 1989, Zayed et al. 1990, Seidler et al.
1996, Gorell et al. 1997, Gorell et al. 1999, Rybicki et al. 1999, Kuhn et al. 1998, Lai et
al. 2002). During the past few years, special attention was paid to aluminium. As it will
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