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Considerable evidence supports roles for calcium-regulating systems and altered
calcium homeostasis in neurodegenerative disorders (Gibson and Peterson, 1987 [1]
Mattson, 1989 [2]; Khachaturian, 1989 [3]).
Cellular degeneration is accompanied by impaired Ca(2+)
homeostasis and a protective role for Ca(2+) binding proteins in certain neuron
populations has been postulated (Heizmann and Braun, 1992 [4]).
It has been assumed
that neurons containing certain intracellular Ca(2+) binding proteins may have a
greater capacity to buffer Ca(2+) and could be more resistant to degeneration (Scharfman
and Schwartzkroin, 1989 [5]).
Disturbances in calcium homeostasis have been observed
to be associated with Alzheimer’s disease (AD) and other neurodegenerative diseases.
Increased total calcium levels and reductions of calcium-binding proteins (calbindin-28k
and calmodulin) have been found in AD brains (Sutherland et al., 1993 [6]).
McLachlan et al. and Sutherland et al. discovered that in AD brains, the CaBP, calmodulin,
was shown to be significantly diminished (McLachlan et al. 1987 [7];
Sutherland et al., 1993 [8]).
Huntington's disease (HD) is also dependent upon the correct functioning
of the basal ganglia. The degeneration of neurons in the basal ganglia is thought
to be due to excitotoxic activity related to an increase in intracellular calcium.
As a result of this insult, increased levels of the calcium-binding proteins parvalbumin
and calbindin D-28k has been noted in the assaulted areas (Parent et al., 1995 [9];
Huang et al., 1995 [10]). In Huntington's Chorea there is significant loss of calbindin-containing
neurons in the basal ganglia (Seto-Oshima et al., 1988 [11]; Ichimiya et al., 1988 [12]).
Parkinson’s disease (PD) is also affected by a rise in intracellular calcium concentrations.
The calcium-binding protein calretinin has been suggested as having a neuroprotective
role in dopaminergic cell groups (Mouatt-Prigent et al., 1994 [13]).
Decreases in calbindin-D28k
in the basal ganglia have been found in cases of PD suggesting a neuroprotective
function in the disease (Iacopino and Christakos, 1989 [14]).
Calbindin containing subpopulations
of neurons in the substantia nigra are spared in PD (Yamada et al., 1990 [15]) and in
an animal model of the disease (Iacopino et al., 1992 [16]).
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