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

INTRODUCTION
be largely discussed later, its ubiquity and extensive use in products and processes
coupled with its reported ability to cause neurodegeneration have made aluminium a
cause of health concern (Exley 1999, Yokel 2000, Zatta et al. 2003, Kawahara 2005).
Potential theories
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Experimental models of PD, epidemiologic studies, neuropathologic
investigations, and genetic analyses, which implicated both environmental and genetic
factors in the pathogenesis of PD, provided important insights into the pathogenesis of
PD (Beal 2001, Betarbet et al. 2002, Dawson and Dawson 2003, Siderowf and Stern
2003). But the exact causative pathogenic pathway(s) for the development of PD
remain(s) hard to demonstrate. Several hypotheses aiming to explain the cause and
beginnings of PD have been proposed.
The “dual-hit” hypothesis
The “dual-hit” hypothesis proposed that a hitherto unknown neurotrophic
pathogen induces the pathological process causing PD and triggering the sequential
involvement of vulnerable regions (Hawkes et al. 2007). This pathogen may enter the
brain via two routes: nasal, with anterograde progression to the amygdala and temporal
lobe; or gastric, by subsequent retrograde and transneuronal transport.
The “multiple hit or multihit” hypothesis
The “multiple hit or multihit” hypothesis points to the idea that PD, originally
identified as a DA-deficit disorder, is probably a multietiological disease resulting of the
combination of multiple interlinking combinated factors or insults acting together
(Sulzer 2007). As assumed by Lang and colleagues, a disease with various contributing
etiologic issues could have several diverse ways of onset and progression (Lang et al.
2007) and this could explain the interindividual clinical and neuropathological
heterogeneity observed in the course of PD. It is important to note that this supposition