title: What is the role of amyloid precursor protein dimerization?
abstract: Extensive research efforts have been conducted over the past decades to understand the processing of the Amyloid Precursor Protein (APP). APP cleavage leads to the production of the beta-amyloid peptide (Abeta), which is the major constituent of the amyloid core of senile plaques found in the brains of patients with Alzheimer disease (AD). Abeta is produced by the sequential cleavage of APP by beta- and gamma-secretases. Cleavage of APP by gamma-secretase also generates the APP Intracellular C-terminal Domain (AICD) peptide, which might be involved in regulation of gene transcription. Up to now, our understanding of the mechanisms controlling APP processing has been elusive. Recently, APP was found to form homo- or hetero-complexes with the APP-like proteins (APLPs), which belong to the same family and share some important structural properties with receptors having a single membrane spanning domain. Homodimerization of APP is driven by motifs present in the extracellular domain and possibly in the juxtamembrane and transmembrane (JM/TM) domains of the protein. These striking observations raise important questions about APP processing and function: How and where is APP dimerizing? What is the role of dimerization in APP processing and function? Can dimerization be targeted by small molecule therapeutics?
authors.affiliation: Université catholique de Louvain, Institute of Neuroscience, Brussels, Belgium.
authors.forename: Naouel Ben
authors.initials: NB
authors.lastname: Khalifa
authors.forename: Joanne
authors.initials: J
authors.lastname: Van Hees
authors.forename: Bernadette
authors.initials: B
authors.lastname: Tasiaux
authors.forename: Sandra
authors.initials: S
authors.lastname: Huysseune
authors.forename: Steven O
authors.initials: SO
authors.lastname: Smith
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
authors.forename: Jean-Noël
authors.initials: JN
authors.lastname: Octave
authors.forename: Pascal
authors.initials: P
authors.lastname: Kienlen-Campard
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019281:Dimerization; D006801:Humans; D008954:Models, Biological
chemical_list: D016564:Amyloid beta-Protein Precursor
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