title: Gene expression profiles of APP and BACE1 in Tg SOD1G93A cortical cells.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse model (Tg SOD1G93A) shows pathological features that closely mimic those seen in ALS patients. An hypothetic link between AD and ALS was suggested by finding an higher amount of amyloid precursor protein (APP) in the spinal cord anterior horn neurons, and of Abeta peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer's disease, as APP, beta- and gamma-secretase, in an animal model of ALS, to understand some possible common molecular mechanisms between these two pathologies. For gene expression analysis, we carried out a quantitative RT-PCR in ALS mice and in transgenic mice over-expressing human wild-type SOD1 (Tg hSOD1). We found that APP and BACE1 mRNA levels were increased 1.5-fold in cortical cells of Tg SOD1G93A mice respect to Tg hSOD1, whereas the expression of gamma-secretase genes, as PSEN1, PSEN2, Nicastrin, and APH1a, showed no statistical differences between wild-type and ALS mice. Biochemical analysis carried out by immunostaining and western blotting, did not show any significant modulation of the protein expression compared to the genes, suggesting the existence of post-translational mechanisms that modify protein levels.
authors.affiliation: Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina, Elena 299, Rome, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Spadoni
authors.forename: Alessio
authors.initials: A
authors.lastname: Crestini
authors.forename: Paola
authors.initials: P
authors.lastname: Piscopo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Malvezzi-Campeggi
authors.forename: Irene
authors.initials: I
authors.lastname: Carunchio
authors.forename: Massimo
authors.initials: M
authors.lastname: Pieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Zona
authors.forename: Annamaria
authors.initials: A
authors.lastname: Confaloni
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology* / Q000201:enzymology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse