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

Ageing
INTRODUCTION
Ageing remains an important risk factor of PD. It is associated with a decline of
pigmented neurons in the SNpc (McGeer et al. 1977) and a decline in striatal DA
transporters (Van Dyck et al. 2002) but no difference between the caudate and putamen
as seen in PD. Even if the incidence of PD is known to increase with age, this disease is
not a simple acceleration of ageing as the pattern of neuronal loss in SN in PD patients
and in the normal aging population differs substantially (Kish et al. 1992).
Role of environmental exposure
Exposure to environmental factors may strongly influence risk of PD.
Environmental factors have also been implicated in the pathogenesis of PD with varying
degrees of association. These include environmental toxins, occupation, dietary factors,
drug use and metals amongst others.
An example of environmental toxin: MPTP
The environmental toxin hypothesis considers that PD-related neurodegeneration
is a consequence from exposure to a DAergic neurotoxin. MPTP (1-methyl-4-phenyl-
1,2,3,6-tetrahydropyridine) is a prototypic example of how an exogenous toxin can
mimic the clinical and pathological features of PD. Davis et al. (1979) and Langston et
al. (1983) were the first to convincingly demonstrate the link between environmental
toxin exposure and the development of PD. They observed that, after illicit drug
consumption, a series of patients developed physical symptoms consistent with PD, and
acute levodopa-responsive parkinsonism. In one case, substantial damage to nigral
neurones was observed (Davis et al. 1979). Analysis of the drug used revealed a
contamination with two side products, MPTP and MPPP (1-methyl-4-phenyl-4-
propionoxy-piperidine) in the synthesis of a meperidine analogue (Langston and Ballard
1983). The causative link between MPTP and the parkinsonian syndrome observed in
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