Journal Article (Review Article)

DZNE-2020-02840

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Alpha-secretase cleavage of the amyloid precursor protein: proteolysis regulated by signaling pathways and protein trafficking.

Lichtenthaler, S. (First author)DZNE*

2012
Bentham Science Publ. Ltd. Hilversum

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Please use a persistent id in citations: doi:10.2174/156720512799361655

Abstract: α-secretase is the name for a metalloprotease activity, which is assumed to play a key role in the prevention of the molecular mechanisms underlying Alzheimer's disease (AD). Proteases similar to α-secretase are essential for a wide range of biological processes, such as cell adhesion and embryonic development. The molecular culprit in AD is the amyloid β peptide (Aβ), which derives from the amyloid precursor protein (APP) through sequential cleavage by the two proteases β- and γ-secretase. In contrast, α-secretase, which is the metalloprotease ADAM10, cleaves APP within the Aβ domain, thus preventing Aβ generation. Additionally, it produces a secreted APP ectodomain with neurotrophic and neuroprotective properties. An increase in α-secretase cleavage is considered a therapeutic approach for AD, but the molecular mechanisms regulating α-secretase cleavage are only partly known. Protein kinase C and mitogen-activated protein kinase constitute central signaling hubs for the regulation of α-secretase cleavage. Additionally, recent studies increasingly demonstrate that the correct spatial and temporal localization of the two membrane proteins APP and α-secretase is essential for efficient α-secretase cleavage of APP. This review highlights the role of signaling pathways and protein trafficking in the control of APP α-secretase cleavage.

Keyword(s): ADAM Proteins: genetics (MeSH) ; ADAM Proteins: metabolism (MeSH) ; ADAM10 Protein (MeSH) ; Alzheimer Disease (MeSH) ; Amyloid Precursor Protein Secretases: genetics (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Animals (MeSH) ; Humans (MeSH) ; Membrane Proteins: genetics (MeSH) ; Membrane Proteins: metabolism (MeSH) ; Protein Transport (MeSH) ; Proteolysis (MeSH) ; Signal Transduction: physiology (MeSH) ; APP protein, human ; Amyloid beta-Protein Precursor ; Membrane Proteins ; Amyloid Precursor Protein Secretases ; ADAM Proteins ; ADAM10 Protein ; ADAM10 protein, human

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Contributing Institute(s):

1. Neuroproteomics (AG Lichtenthaler)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; BIOSIS Reviews Reports And Meetings ; Clarivate Analytics Master Journal List ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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