title: Membrane trafficking pathways in Alzheimer's disease.
abstract: Membrane proteins are constantly being trafficked in cells and the relevant proteins in Alzheimer's disease (AD), such as the amyloid precursor protein (APP) and its processing enzymes, are not exempted from that. Molecular cell biologists have been endeavoring to ascertain a roadmap for APP processing and trafficking in various cell types including neurons. This has led to the identification of numerous regulatory sorting mechanisms, protein-protein interactions and lipidic microenvironments that largely define how and where the substrate APP meets its processing enzymes. However, the cell biology of tau, and the formation of neurofibrillary tangles, has long been regarded as a separate field. Nonetheless, recent progress is bringing both worlds together in a new paradigm on how Aβ toxicity and tau are physiologically connected. Here, we discuss an update of our current appraisal on how membrane trafficking may play an important role in the pathogenesis of the disease and how this could be exploited for effective therapy.
authors.affiliation: Systems and Cell Biology of Neurodegeneration, Division of Psychiatry Research, University of Zurich, August-Forel Str. 1, Zurich 8008, Switzerland. rajendran@bli.uzh.ch
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rajendran
authors.forename: Wim
authors.initials: W
authors.lastname: Annaert
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human