Abstract
The predominant degeneration of cholinergic neurons extending from the nucleus basalis of Meynert suggests that retarding the loss of cholinergic function may prove palliative in the treatment of Alzheimer’s disease. Use of selective acetylcholinesterase (AChE) inhibitors which are retained within the central nervous system is one widely considered approach. An alternative approach would be regulation of expression of proteins critical to cholinergic nervous system function. However, this approach, to be most effective, would require adjustment of subtle differences in gene expression. For example, enhancement of the transport and enzymatic processes involved in acetylcholine biosynthesis concomitant with a decrease in AChE expression might be therapeutically beneficial in facilitating the availability of neurotransmitter. However, AChE may play a role in the development of the nervous system (Layer and Sporns, 1987) and in the maintenance of synaptic and heterologous cell contacts (DeLa Escalera et al., 1990). Thus, a rational approach to therapeutic intervention in Alzheimer’s disease requires a detailed knowledge of the potential target. Recombinant DNA technology should prove useful in this regard. Already expression of cloned genes provides sources of human AChE (Soreq et al., 1990; Li et al., 1991) and site-directed mutants (Gibney et al., 1990; Soreq et al., 1991) add a new dimension to structure-activity relationships. Moreover, recombinant techniques should define selective trophic factors and trans-activating factors which influence expression of gene products essential to neurotransmission. In this chapter we describe a target of therapeutic attack, AChE, and how expression of its gene is regulated.
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Taylor, P., Li, Y., Camp, S., Rachinsky, T.L., Getman, D. (1991). Structure of the Acetylcholinesterase Gene: Regulation of Its Expression. In: Becker, R., Giacobini, E. (eds) Cholinergic Basis for Alzheimer Therapy. Advances in Alzheimer Disease Therapy. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4899-6738-1_6
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DOI: https://doi.org/10.1007/978-1-4899-6738-1_6
Publisher Name: Birkhäuser, Boston, MA
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