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Gene Expression Profiles of APP and BACE1 in Tg SOD1G93A Cortical Cells

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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 Aβ peptides in ALS patients skin. In this work, we have investigated the expression of some genes involved in Alzheimer’s disease, as APP, β- and γ-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 γ-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.

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Abbreviations

APP:

Amyloid precursor protein

BACE1:

β-Site APP cleaving enzyme

ALS:

Amyotrophic lateral sclerosis

CNS:

Central nervous system

PSEN1:

Presenilin 1

PSEN2:

Presenilin 2

NCSTN:

Nicastrin

APH1:

Anterior pharynx defective 1

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Acknowledgement

This work was supported by MIUR Italy (FIRB: contract RBAU01A7T4 to C.Z.)

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Authors and Affiliations

  1. Department of Cellular Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina, Elena 299, Rome, Italy

    Ornella Spadoni, Alessio Crestini, Paola Piscopo, Lorenzo Malvezzi-Campeggi & Annamaria Confaloni

  2. Department of Neuroscience, University of Rome “Tor Vergata” and Fondazione S. Lucia, Rome, Italy

    Irene Carunchio, Massimo Pieri & Cristina Zona

Authors
  1. Ornella Spadoni
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  2. Alessio Crestini
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  3. Paola Piscopo
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  4. Lorenzo Malvezzi-Campeggi
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  5. Irene Carunchio
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  6. Massimo Pieri
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  7. Cristina Zona
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  8. Annamaria Confaloni
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Correspondence to Annamaria Confaloni.

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Spadoni, O., Crestini, A., Piscopo, P. et al. Gene Expression Profiles of APP and BACE1 in Tg SOD1G93A Cortical Cells. Cell Mol Neurobiol 29, 635–641 (2009). https://doi.org/10.1007/s10571-009-9356-8

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  • DOI: https://doi.org/10.1007/s10571-009-9356-8

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