Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits
gamma-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein, catalyzing the formation of amyloid beta peptides that form amyloid plaques, which contribute to Alzheimer’s disease pathogenesis. gamma-Secretase also cleaves Notch, among many other type I trans...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-01-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00342/full |
| _version_ | 1818618327780556800 |
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| author | Natalya eGertsik Danica eChiu Yueming eLI |
| author_facet | Natalya eGertsik Danica eChiu Yueming eLI |
| author_sort | Natalya eGertsik |
| collection | DOAJ |
| description | gamma-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein, catalyzing the formation of amyloid beta peptides that form amyloid plaques, which contribute to Alzheimer’s disease pathogenesis. gamma-Secretase also cleaves Notch, among many other type I transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity, gamma-secretase activity is tightly regulated. This regulation is a function of many cellular entities, including but not limited to the essential gamma-secretase subunits, nonessential (modulatory) subunits, and gamma-secretase substrates. Regulation is also accomplished by an array of cellular events, such as presenilin (active subunit of gamma-secretase) endoproteolysis and hypoxia. In this review we discuss how gamma-secretase is regulated with the hope that an advanced understanding of these mechanisms will aid in the development of effective therapeutics for gamma-secretase-associated diseases like Alzheimer’s disease and Notch-addicted cancer |
| first_indexed | 2024-12-16T17:19:50Z |
| format | Article |
| id | doaj.art-5af529cdccd643d7b6b76a8340942b88 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-16T17:19:50Z |
| publishDate | 2015-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-5af529cdccd643d7b6b76a8340942b882022-12-21T22:23:11ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652015-01-01610.3389/fnagi.2014.00342127941Complex Regulation of gamma-Secretase: from Obligatory to Modulatory SubunitsNatalya eGertsik0Danica eChiu1Yueming eLI2Memorial Sloan-Kettering Cancer CenterMemorial Sloan-Kettering Cancer CenterMemorial Sloan-Kettering Cancer Centergamma-Secretase is a four subunit, 19-pass transmembrane enzyme that cleaves amyloid precursor protein, catalyzing the formation of amyloid beta peptides that form amyloid plaques, which contribute to Alzheimer’s disease pathogenesis. gamma-Secretase also cleaves Notch, among many other type I transmembrane substrates. Despite its seemingly promiscuous enzymatic capacity, gamma-secretase activity is tightly regulated. This regulation is a function of many cellular entities, including but not limited to the essential gamma-secretase subunits, nonessential (modulatory) subunits, and gamma-secretase substrates. Regulation is also accomplished by an array of cellular events, such as presenilin (active subunit of gamma-secretase) endoproteolysis and hypoxia. In this review we discuss how gamma-secretase is regulated with the hope that an advanced understanding of these mechanisms will aid in the development of effective therapeutics for gamma-secretase-associated diseases like Alzheimer’s disease and Notch-addicted cancerhttp://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00342/fullgamma-secretaseAlzheimer’s diseaseAPPHIF-1alphaNotchPresenilin |
| spellingShingle | Natalya eGertsik Danica eChiu Yueming eLI Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits Frontiers in Aging Neuroscience gamma-secretase Alzheimer’s disease APP HIF-1alpha Notch Presenilin |
| title | Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits |
| title_full | Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits |
| title_fullStr | Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits |
| title_full_unstemmed | Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits |
| title_short | Complex Regulation of gamma-Secretase: from Obligatory to Modulatory Subunits |
| title_sort | complex regulation of gamma secretase from obligatory to modulatory subunits |
| topic | gamma-secretase Alzheimer’s disease APP HIF-1alpha Notch Presenilin |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00342/full |
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