title: Analysis of amyloid precursor protein function in Drosophila                      melanogaster.
abstract: Amyloid precursor proteins (APPs) are evolutionary conserved from nematodes to man (Jacobsen and Iverfeldt in Cell Mol Life Sci 66:2299-2318, 2009) suggesting an important physiological function of these proteins. Human APP is a key factor in the pathogenesis of Alzheimer's Disease because its proteolytic processing results in the production of the neurotoxic Aβ-peptide, which accumulates in the amyloid plaques characteristic for this disease (Selkoe in Physiol Rev 81(2):741-766, 2001). However, the processing also leads to the production of several other fragments and the role of these products, as well as the function of the full-length protein is so far not well understood. The functional analysis of APP in vertebrates has been hampered by the fact that two close relatives, APLP1 and APLP2, exist and that knock-out mice for APP only show subtle defects. In contrast, invertebrates like Caenorhabditis                         elegans and Drosophila express only one APP-like protein but whereas a null mutation in the C. elegans APL-1 protein is lethal, flies lacking APPL (Amyloid Precursor Protein-like) are viable but show synaptic defects and behavioral abnormalities. Together with the analyses of flies that express APP proteins ectoptically or xenotopically, these studies show that APP proteins are involved in neuronal differentiation, neuritic outgrowth, and synapse formation. In addition, they play a role in long-term memory formation and maintaining brain integrity in adult flies.
authors.affiliation: Institut für Zoologie III-Neurobiologie, Johannes Gutenberg-Universität Mainz, Colonel Kleinmann-Weg 2, 55099 Mainz, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Poeck
authors.forename: Roland
authors.initials: R
authors.lastname: Strauss
authors.forename: Doris
authors.initials: D
authors.lastname: Kretzschmar
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D016564:Amyloid beta-Protein Precursor; C066839:Appl protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins