title: [Morphological and functional abnormalities in neuromuscular junctions of Drosophila melanogaster induced by the expression of human APP gene].
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the loss of neurocortical and hippocampal synapses that precedes amyloidosis and neurodegeneration and closely correlates with memory impairment. Mutations in the amyloid precursor protein (APP) cause familial AD and result in the increased production of amyloid-beta-protein (Abeta). To gain insights into synaptic effects of APP, we expressed APP, mutant form APP-Swedish and BACE in the motor neurons of fly larvae. We have shown that targeted expression of APP (APP-Swedish) in Drosophila larval motor neurons causes significant morphological and functional changes in neuromuscular junctions (NMJs): a dramatic increase in the number of synaptic buttons and changes in exocytosis as revealed by incorporation of the styryl dye FM4-64. Analysis of the number and distribution of mitochondria showed that motor neurons overexpressing APP (APP-Swedish) had a significant reduction of functional mitochondria in the presynaptic terminal. Significant synaptic abnormalities were observed for APP (APP-Swedish) and human beta-secretase (BACE) resulting in secretion of amyloid beta protein (Abeta). We suggest that APP participates in regulation of synaptic functions and its elevated expression leads to synaptic pathology independently from neurotoxic effects of Abeta.
authors: S V
authors: SV
authors: Sarantseva
authors: G A
authors: GA
authors: Kislik
authors: N A
authors: NA
authors: Tkachenko
authors: A N
authors: AN
authors: Vasil'ev
authors: A L
authors: AL
authors: Shvartsman
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005089:Exocytosis; D005456:Fluorescent Dyes; D015870:Gene Expression; D006801:Humans; D007814:Larva / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism / Q000648:ultrastructure*; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure*; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C092350:FM 4-64; D005456:Fluorescent Dyes; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D053829:Amyloid Precursor Protein Secretases