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

INTRODUCTION
Cell death pathways
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There is substantial indication that cell death in PD occurs by way of a signal-
mediated apoptotic process (Hirsch et al. 1999, Mattson et al. 2000). Apoptosis is a
mechanism of programmed cell death (PCD) carried out by caspases during which a cell
goes through various morphological changes including membrane blebbing, changes to
the cell membrane such as loss of membrane asymmetry and attachment, cell shrinkage,
nuclear condensation, and DNA fragmentation. A normal functioning of apoptosis
avoids triggering harmful responses, such as inflammation. A great number of apoptotic
pathways are activated in response to PD-induced dysfunction, such as JNK signaling,
induction of Bax, p53 activation, cell cycle re-entry, bcl-2 family signalling, and
caspase activation (Hirsch et al. 1999, Tatton et al. 2003, Nair et al. 2006, Levy et al.
2009). As an example, mutations in LRRK2 are linked to activation of the intrinsic
apoptotic pathway, with cytochrome c released into the cytosol, activation of caspase 3
and nuclear condensation (Iaccarino et al. 2007).