|
The role of calcium in human physiology has been extensively
researched throughout the last century. Disruptions in calcium homeostasis are known to
cause and to correlate with a large number of diseases, syndromes and conditions.
Following much investigation, calcium-binding proteins (CaBPs) have been recognized as
protective factors in neuronal populations susceptible to toxicity via calcium and
calcium-mediated actions. Apoaequorin is from the family of calcium-binding proteins
known as the EF-hand family. Several CaBPs endogenous to the human body are also of
the EF-hand family and have been found to serve protective roles in certain cellular
populations.
|
|
|
Relevance of calcium binding proteins.
CaBPs are important for regulating the intracellular calcium concentration of neurons
(Baimbridge et al., 1992 [1]). In addition, studies have shown that neurons lacking in certain
CaBPs are less able to handle various insults. For example, dissociated cells that are
immunoreactive for the CaBP calbindin are better able to withstand excitatory amino acid
(EAA) insults, suggesting that the presence of calbindin (and perhaps other CaBPs) may serve
important neuroprotective functions (Mattson et al., 1991 [2]).
In addition, numerous studies suggest that there is a selective decrease in certain
CaBPs in the brains of aged animals, including humans
(Ichimiya et al., 1988 [3];
Iacopino and Christakos, 1990 [4];
Hof and Morrison, 1991 [5];
Amenta et al., 1994 [6];
Selden et al., 1994 [7];
Villa et al., 1994 [8];
De Jong et al., 1996 [9];
Zettel et al., 1997 [10];
Moyer et al., 2001 [11]).
Loss of these important CaBPs with advancing age may leave certain populations of neurons
vulnerable to any insult that results in massive or even moderate increases in intracellular
calcium concentrations. The relationship between calcium, neuronal degeneration, CaBPs,
and aging suggest that a viable but untapped treatment plan may involve replenishment of
neuronal CaBPs, particularly in higher brain regions known to degenerate with advancing age,
such as the hippocampus and associated MTL structures
(Visser et al., 2002 [12]).
One such CaBP is apoaequorin, a naturally-occurring calcium-sensitive bioluminescent
protein originally isolated from jellyfish. Administration and uptake of apoaequorin by
neurons may be beneficial for ameliorating the negative effects of excess calcium influx
observed in aged neurons, which may enhance neuron survival and improve cognitive
function in older animals.
|