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

INTRODUCTION
Parkinson diseases: a syndrome of different disorders
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There is a large body of evidence indicating that impairment in protein biology,
mitochondrial dysfunction, neuroinflammation, cell death pathways, excitotoxicity, and
oxidative stress, to cite only some of the most salient, are key pathologic mechanisms in
the etiology of PD, all of which are tightly linked (Figure 17; Mattson 2000, Chung et
al. 2001, Vila and Przedborski 2003, Eriksen et al. 2005, Gandhi and Wood 2005,
Abou-Sleiman et al. 2006, Olanow 2007, Tansey et al. 2007). But none of these
pathogenic mechanisms alone has been proven to be the exact causative and unifying
cytotoxic pathway leading to neurodegeneration in PD (Sulzer 2007). It is now widely
recognized that PD is not a single homogenous disease but to a certain extent a
multifaceted syndrome of different neurological disorders, caused by a complex
interaction between genetic, environmental, and other factors leading to a common final
pathology (Moore et al. 2005, Klein and Schlossmacher 2007, Schapira 2008, Zhou et
al. 2008). Actually, the term Parkinson diseases was proposed to reassess this syndrome
of multiple “parkinsonism types” and remind that multiple etiologies are possible to
explain the patient‟s neurologic syndrome (Weiner 2008). In the future, PD will be
probably subdivided into different varieties and ethiologies, maybe assigning numbers
to each different “parkinsonism types”.
Figure 17: Pathologic mechanisms in the etiology of PD