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

INTRODUCTION
characterized as are lesions in the DAergic systems, the temporal relationship of
damage to specific neurochemical systems is not well established. Although, for
example, some patients develop depression months or years prior to the onset of motor
symptoms, the non-motor symptoms are generally thought to dominate the more severe
or later stages of the disease (Chaudhuri et al. 2006).
Lewy bodies, Lewy neurites and pale bodies
In addition to neuronal loss, another important pathological feature observed in
PD is the presence of fibrillar aggregates, called LB, Lewy neurites (LN) and pale
bodies, in the few remaining surviving nigral DAergic neurons (Dauer and Przedborski
2003, Probst et al. 2008).
There are two morphologic types of LB: the brainstem classical type and the
cortical type. Brainstem-type LB are intraneuronal cytoplasmic inclusions, spherical or
elongated, 5-25 μm in diameter, and possessing a dense eosinophilic core and a clear
peripheral halo (Figure 12A; Duffy and Tennyson 1965, Roy and Wolman 1969,
Pappolla 1986). Cortical LB are also intracytoplasmic inclusions but often irregular in
shape and lacking a distinctive core and conspicuous halo Figure 12B. LN correspond
to abnormal dystrophic neurites that contain filaments similar to those found in LB
(Figure 12C; Dickson et al. 1991). Whereas LB are developed in the perikarya, LN are
located in the neuronal processes (Figure 12D). Pale bodies are rounded well-defined
areas without halos, less eosinophilic, found in melanized cells of the SNpc and the
locus coeruleus. They contain vesicular and granular structures and filaments identical
to those seen in LB. As pale bodies often co-occur with one or more LB in the same
neurons, they have been proposed to represent a stage in the formation of LB.
LB are composed of more than 76 molecules, including numerous proteins, such
as α-synuclein, parkin, ubiquitin, and neurofilaments (Wakabayashi et al. 2007).
Whereas the SNpc appears to be the first region to be affected by neuronal loss, LB are
not confined to the SNpc but can also be found within many of the spared neurons in
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