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

INTRODUCTION
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As mentioned before, aluminium is able to stimulate iron-induced oxidations. In
the peroxidation process both metals are thought to act synergistically: while the
aluminium binding to neuronal membranes is attended to facilitate its attack by iron-
mediated oxidative damage, the subsequent oxidation of the membrane will
consecutively increase its binding to aluminium, hence exacerbating peroxidation
(Figure 22).
Figure 22: Effects of aluminium and iron on the membrane peroxidation (Zatta et al. 2002,
Oteiza et al. 2004)
Lipid peroxidation is particularly active in the brain where it induces: a) changes
in the structure of biological membranes resulting in the loss of membrane fluidity, b)
changes of the structural order of membrane lipids (Palmeira and Oliveira 1992), c)
variations in membrane potential, d) an increase in membrane permeability to ions
(Marshansky et al. 1983), e) modifications in the activity of membrane-bound enzymes
(Pereira et al. 1996), and f) alterations in receptor functions.
Aluminium affects cell signaling
Another mechanism that has been suggested to be involved in aluminium
toxicity is the alteration of specific cell signaling cascades. Aluminium interferes with
phosphoinositide signal transduction pathway (Nostrandt et al. 1996, Quintal-Tun et al.
2007). This metabolic pathway mediated by the enzyme phosphatidylinositol-specific
phospholipase C (PI-PLC) renders inositol triphosphate (IP3) and diacylglycerol, two
important intracellular second messengers. IP3 is in charge of the intracellular