Cell Surface Receptor Mediated Control of Amyloid Precursor Protein Secretion: Involvement of Pleiotropic Signal Transduction Cascades
Amyloid plaques associated with brain vasculature and parenchyma are the pathological hallmark of Alzheimer’s Disease (AD) (Joachim and Selkoe, 1992). The deposits contain a variety of proteins but are mainly composed of a peptide with 39 to 43 amino acids, the ß-amyloid peptide (ß/A4). ß/A4 is derived from the proteolytic processing of a larger protein, the amyloid precursor protein (APP). APP is a family of membrane associated glycoproteins that are constitutively synthesized by a variety of cells including neurons and glia (Estus et al., 1992; Shoji et al., 1992; Busciglio et al., 1993). Proteolytic cleavage at a single site in its ß/A4 region releases the majority of APP from cells and at the same time eliminates the production of ß/A4 (Weidemann et al., 1989; Anderson et al., 1992). Alternatively, APP is processed by a second pathway that leads to the formation of intact, amyloidogenic ß/A4 (Haass et al., 1991; Golde et al., 1992; Hung et al., 1992). Cells normally produce small amounts of ß/A4, but genetic mutations (Cai et al., 1993a; Haass et al., 1993) and trauma (Roberts et al., 1991) can enhance the expression of the peptide.
KeywordsMuscarinic Receptor Chinese Hamster Ovary Cell Chinese Hamster Ovary Muscarinic Agonist Muscarinic Receptor Subtype
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