Please use this identifier to cite or link to this item: doi:10.22028/D291-27426
Title: Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
Author(s): Grimm, Marcus O.W.
Haupenthal, Viola J.
Rothhaar, Tatjana L.
Zimmer, Valerie C.
Grösgen, Sven
Hundsdörfer, Benjamin
Lehmann, Johannes
Grimm, Heike S.
Hartmann, Tobias
Language: English
Title: International Journal of Molecular Sciences
Volume: 14
Issue: 3
Startpage: 5879
Endpage: 5898
Publisher/Platform: MDPI
Year of Publication: 2013
DDC notations: 610 Medicine and health
Publikation type: Journal Article
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 influence APP processing. Although several studies have focused on γ-secretase, the effect of the membrane lipid microenvironment on α-secretase is poorly understood. In the present study, we systematically investigated the effect of fatty acid (FA) acyl chain length (10:0, 12:0, 14:0, 16:0, 18:0, 20:0, 22:0, 24:0), membrane polar lipid headgroup (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine), saturation grade and the FA double-bond position on α-secretase activity. We found that α-secretase activity is significantly elevated in the presence of FAs with short chain length and in the presence of polyunsaturated FAs, whereas variations in the phospholipid headgroups, as well as the double-bond position, have little or no effect on α-secretase activity. Overall, our study shows that local lipid membrane composition can influence α-secretase activity and might have beneficial effects for AD.
DOI of the first publication: 10.3390/ijms14035879
Link to this record: urn:nbn:de:bsz:291--ds-274263
hdl:20.500.11880/28521
http://dx.doi.org/10.22028/D291-27426
ISSN: 1422-0067
Date of registration: 3-Jan-2020
Faculty: M - Medizinische Fakultät
Department: M - Neurologie und Psychiatrie
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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