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

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...
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Autor*in:	Heike S. Grimm [verfasserIn] Tobias Hartmann [verfasserIn] Johannes Lehmann [verfasserIn] Benjamin Hundsdörfer [verfasserIn] Sven Grösgen [verfasserIn] Valerie C. Zimmer [verfasserIn] Tatjana L. Rothhaar [verfasserIn] Viola J. Haupenthal [verfasserIn] Marcus O. W. Grimm [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 14(2013), 3, Seite 5879-5898
Übergeordnetes Werk:	volume:14 ; year:2013 ; number:3 ; pages:5879-5898

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/ijms14035879

Katalog-ID:	DOAJ044790600

Internformat


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520			\|a 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.
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allfields	10.3390/ijms14035879 doi (DE-627)DOAJ044790600 (DE-599)DOAJ427f4cfb366f4035ac5a11123c7c8e72 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Heike S. Grimm verfasserin aut Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry Tobias Hartmann verfasserin aut Johannes Lehmann verfasserin aut Benjamin Hundsdörfer verfasserin aut Sven Grösgen verfasserin aut Valerie C. Zimmer verfasserin aut Tatjana L. Rothhaar verfasserin aut Viola J. Haupenthal verfasserin aut Marcus O. W. Grimm verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 14(2013), 3, Seite 5879-5898 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:14 year:2013 number:3 pages:5879-5898 https://doi.org/10.3390/ijms14035879 kostenfrei https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 kostenfrei http://www.mdpi.com/1422-0067/14/3/5879 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2013 3 5879-5898
spelling	10.3390/ijms14035879 doi (DE-627)DOAJ044790600 (DE-599)DOAJ427f4cfb366f4035ac5a11123c7c8e72 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Heike S. Grimm verfasserin aut Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry Tobias Hartmann verfasserin aut Johannes Lehmann verfasserin aut Benjamin Hundsdörfer verfasserin aut Sven Grösgen verfasserin aut Valerie C. Zimmer verfasserin aut Tatjana L. Rothhaar verfasserin aut Viola J. Haupenthal verfasserin aut Marcus O. W. Grimm verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 14(2013), 3, Seite 5879-5898 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:14 year:2013 number:3 pages:5879-5898 https://doi.org/10.3390/ijms14035879 kostenfrei https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 kostenfrei http://www.mdpi.com/1422-0067/14/3/5879 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2013 3 5879-5898
allfields_unstemmed	10.3390/ijms14035879 doi (DE-627)DOAJ044790600 (DE-599)DOAJ427f4cfb366f4035ac5a11123c7c8e72 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Heike S. Grimm verfasserin aut Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry Tobias Hartmann verfasserin aut Johannes Lehmann verfasserin aut Benjamin Hundsdörfer verfasserin aut Sven Grösgen verfasserin aut Valerie C. Zimmer verfasserin aut Tatjana L. Rothhaar verfasserin aut Viola J. Haupenthal verfasserin aut Marcus O. W. Grimm verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 14(2013), 3, Seite 5879-5898 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:14 year:2013 number:3 pages:5879-5898 https://doi.org/10.3390/ijms14035879 kostenfrei https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 kostenfrei http://www.mdpi.com/1422-0067/14/3/5879 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2013 3 5879-5898
allfieldsGer	10.3390/ijms14035879 doi (DE-627)DOAJ044790600 (DE-599)DOAJ427f4cfb366f4035ac5a11123c7c8e72 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Heike S. Grimm verfasserin aut Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry Tobias Hartmann verfasserin aut Johannes Lehmann verfasserin aut Benjamin Hundsdörfer verfasserin aut Sven Grösgen verfasserin aut Valerie C. Zimmer verfasserin aut Tatjana L. Rothhaar verfasserin aut Viola J. Haupenthal verfasserin aut Marcus O. W. Grimm verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 14(2013), 3, Seite 5879-5898 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:14 year:2013 number:3 pages:5879-5898 https://doi.org/10.3390/ijms14035879 kostenfrei https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 kostenfrei http://www.mdpi.com/1422-0067/14/3/5879 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2013 3 5879-5898
allfieldsSound	10.3390/ijms14035879 doi (DE-627)DOAJ044790600 (DE-599)DOAJ427f4cfb366f4035ac5a11123c7c8e72 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Heike S. Grimm verfasserin aut Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry Tobias Hartmann verfasserin aut Johannes Lehmann verfasserin aut Benjamin Hundsdörfer verfasserin aut Sven Grösgen verfasserin aut Valerie C. Zimmer verfasserin aut Tatjana L. Rothhaar verfasserin aut Viola J. Haupenthal verfasserin aut Marcus O. W. Grimm verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 14(2013), 3, Seite 5879-5898 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:14 year:2013 number:3 pages:5879-5898 https://doi.org/10.3390/ijms14035879 kostenfrei https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 kostenfrei http://www.mdpi.com/1422-0067/14/3/5879 kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2013 3 5879-5898
language	English
source	In International Journal of Molecular Sciences 14(2013), 3, Seite 5879-5898 volume:14 year:2013 number:3 pages:5879-5898
sourceStr	In International Journal of Molecular Sciences 14(2013), 3, Seite 5879-5898 volume:14 year:2013 number:3 pages:5879-5898
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Heike S. Grimm @@aut@@ Tobias Hartmann @@aut@@ Johannes Lehmann @@aut@@ Benjamin Hundsdörfer @@aut@@ Sven Grösgen @@aut@@ Valerie C. Zimmer @@aut@@ Tatjana L. Rothhaar @@aut@@ Viola J. Haupenthal @@aut@@ Marcus O. W. Grimm @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ044790600
language_de	englisch
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callnumber-first	Q - Science
author	Heike S. Grimm
spellingShingle	Heike S. Grimm misc QH301-705.5 misc QD1-999 misc Alzheimer’s disease misc α-secretase misc ADAM10 misc lipids misc phospholipids misc chain length misc saturation misc headgroup misc Biology (General) misc Chemistry Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
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topic_title	QH301-705.5 QD1-999 Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease Alzheimer’s disease α-secretase ADAM10 lipids phospholipids chain length saturation headgroup
topic	misc QH301-705.5 misc QD1-999 misc Alzheimer’s disease misc α-secretase misc ADAM10 misc lipids misc phospholipids misc chain length misc saturation misc headgroup misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc Alzheimer’s disease misc α-secretase misc ADAM10 misc lipids misc phospholipids misc chain length misc saturation misc headgroup misc Biology (General) misc Chemistry
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title	Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
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title_full	Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
author_sort	Heike S. Grimm
journal	International Journal of Molecular Sciences
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author_browse	Heike S. Grimm Tobias Hartmann Johannes Lehmann Benjamin Hundsdörfer Sven Grösgen Valerie C. Zimmer Tatjana L. Rothhaar Viola J. Haupenthal Marcus O. W. Grimm
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title_sort	effect of different phospholipids on α-secretase activity in the non-amyloidogenic pathway of alzheimer’s disease
callnumber	QH301-705.5
title_auth	Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Effect of Different Phospholipids on α-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease
url	https://doi.org/10.3390/ijms14035879 https://doaj.org/article/427f4cfb366f4035ac5a11123c7c8e72 http://www.mdpi.com/1422-0067/14/3/5879 https://doaj.org/toc/1422-0067
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