Analysis of amyloid precursor protein function in Drosophila melanogaster

Burkhard Poeck, Roland Strauss, Doris Kretzschmar

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalExperimental Brain Research
Volume217
Issue number3-4
DOIs
StatePublished - Apr 2012

Keywords

  • APP proteins
  • Drosophila

ASJC Scopus subject areas

  • Neuroscience(all)

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