Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease.docVIP

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Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease.doc

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Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease

Int. J. Mol. Sci. 2013, 14, 5879-5898; doi:10.3390/ijmOPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease Marcus O. W. Grimm 1,2,3,?,*, Viola J. Haupenthal , Tatjana L. Rothhaar 1, 1,? Valerie C. Zimmer , Sven Gr?sgen , Benjamin Hundsd?rfer , Johannes Lehmann 1, 1 1 1 1 Heike S. Grimm and Tobias Hartmann 1,2,3 1 Experimental Neurology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany; E-Mails: viola.haupenthal@uniklinikum-saarland.de (V.J.H.); tatjana.rothhaar@uks.eu (T.L.R.); valerie-zimmer@web.de (V.C.Z.); sven.groesgen@uks.eu (S.G.); benjamin.hundsdoerfer@uks.eu (B.H.); lehmannjohannes87@web.de (J.L.); heike.grimm@gmx.de (H.S.G.); tobias.hartmann@uniklinikum-saarland.de (T.H.) 2 Neurodegeneration and Neurobiology, Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany 3 Deutsches Institut für DemenzPr?vention (DIDP), Saarland University, Kirrberger Str. 1, 66421 Homburg/Saar, Germany ? These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: marcus.grimm@uks.eu; Tel.: +49-6841-1647919; Fax: +49-6841-1647925. Received: 13 December 2012; in revised form: 19 January 2013 / Accepted: 1 March 2013 / Published: 13 March 2013 Abstract: Alzheimer’s disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic target for AD treatment. APP and the APP-cleaving secretases are all transmembrane proteins, thus local membrane lipid composition is proposed to