In Vivo Biology of APP and its Homologues
A principal pathological feature of Alzheimer’s disease is the deposition of ß-amyloid protein (Aß) in brain parenchyma.1–3 Aß, an ~4-kD polypeptide, is derived from larger type I integral membrane glycoproteins, termed the amyloid precursor proteins (APP).4–9 APP is a member of a family of homologous amyloid precursor-like proteins (APLPs), including APLP110 and APLP2.11–13 APP, APLP1, and APLP2 show considerable homology in the N-terminal cysteine-rich domain, the cytoplasmic tail and transmembrane sequences, but the APLPs differ from APP by the conspicuous absence of the Aß region. APP homologues have also been identified in C. elegans (apl-l)14 and Drosophila (appl),15 and these molecules lack the Aß region as well. Flies with a deleted APPL gene are viable and have a defective fast phototaxis response, a behavior that is partially rescued by the introduction of human APP cDNA. The biological functions of APP and the APLPs in the mammalian nervous system are far from clear, although several studies have suggested that APP play roles in cell-cell or cell-matrix interactions,16–18 calcium hemostasis,19 growth promoting activities,20 and the formation/maintenance of synapses in vivo. 21 More recently, investigations in cultured cells22 and in transgenic animals23 have provided support to the notion that APP is neuroprotective.
KeywordsOlfactory Bulb Amyloid Precursor Protein Olfactory Epithelium Human Amyloid Precursor Protein Chondroitin Sulfate Glycosaminoglycan
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