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

INTRODUCTION
Aluminium influx and efflux into the brain
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The brain has lower aluminium concentrations (about 1%) than many other
tissues (Yokel and McNamara 2001), but it is an important target organ for aluminium-
toxicity. Even as the BBB is highly selective to a great variety of substances, including
metals, aluminium is able to cross it and enter the brain from blood (Yokel 2002b) and
to accumulate in nerve and glial cells. Although the mechanism(s) responsible for
aluminium transport at the BBB has not been clarified yet, it has been reported that
aluminium can penetrate into the brain as a complex with transferrin by a receptor-
mediated endocytosis (Roskams and Connor 1990) and also bound to citrate via a
specific transporter, being the system Xc � (L-glutamate/L-CySH exchanger) the most
recently accepted candidate (Nagasawa et al. 2005). There is also evidence for
transporter-mediated efflux from the brain, the organic anion transporting polypeptide
(oatp) family was suggested to be a candidate (Yokel 2006).
The existence of a long apparent half-life of aluminium in brain tissue has been
used to explain its easy accumulation into the brain following aluminium administration
(Yokel et al. 2001b, Baydar et al. 2003, Sánchez-Iglesias et al. 2007b). The elimination
half-life of aluminium from human brain is calculated to be seven years (Yokel and
McNamara 2001). This assumption and the long life of neurons could be involved in the
elevated levels of aluminium found in the brain of some patients suffering PD (Hirsh et
al. 1991, Good et al. 1992, Yasui et al. 1992) and AD (Crapper et al. 1973, Perl and
Brody 1980), a statement that, on the other hand, will not be understoo as the principal
cause of those disorders.
Since aluminium and its compounds are widely distributed in the environment
(food, drinking water, airborne contaminants) and extensively used in a variety of
products and processes (antiperspirants, antacids, intravenous solutions), it has aroused
considerable health concern, due to both its common exposure and its particularly
reported ability to cause neurodegeneration (Exley 1999, Yokel 2000, Zatta et al. 2003,
Kawahara 2005). As we have previously seen, the daily reported mean dietary intake of