Unraveling in vivo Functions of Amyloid Precursor Protein: Insights from Knockout and Knockdown StudiesSenechal Y. · Larmet Y. · Dev K.K.
aNeuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland; bLaboratoire de Signalisations Moleculaires et Neurodegenerescence, Faculté de Medecine, INSERM, U692, Université Louis-Pasteur, Strasbourg, France
The amyloid precursor protein (APP) is a widely expressed transmembrane protein that is cleaved to generate Aβ peptides in the central nervous system and is a key player in the pathogenesis of Alzheimer’s disease. The precise biological functions of APP still remain unclear although various roles have been proposed. While a commonly accepted model argues that Aβ peptides are the cause of onset and early pathogenesis of Alzheimer’s disease, recent discussions challenge this ‘Aβ hypothesis’ and suggest a direct role for APP in this neurodegenerative disease. Loss-of-function studies are an efficient way to elucidate the role of proteins and concurrently a variety of in vitro and in vivo studies has been performed for APP where protein levels have been downregulated and functional consequences monitored. Complete disruption of APP gene expression has been achieved by the generation of APP knockout animal models. Further knockdown studies using antisense and RNA interference have allowed scientists to reduce APP expression levels and have opened new avenues to explore the physiological roles of APP. In the present review, we focus on knockout and knockdown approaches that have provided insights into the physiological functions of APP and discuss their advantages and drawbacks.
Kumlesh K. Dev
Novartis Institutes for BioMedical Research
Novartis Pharma AG, WSJ 386-7-43
CH–4002 Basel (Switzerland)
Tel. +41 61 324 2942, Fax +41 61 324 8381, E-Mail firstname.lastname@example.org
Number of Print Pages : 14
Number of Figures : 3, Number of Tables : 2, Number of References : 119
Vol. 3, No. 3, Year 2006 (Cover Date: September 2006)
Journal Editor: Nitsch, R.M. (Zürich)
ISSN: 1660–2854 (print), 1660–2862 (Online)
For additional information: http://www.karger.com/NDD