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Presenilins and γ-Secretase in Membrane Proteostasis

Department of Neurology, University of Bonn, 53127 Bonn, Germany
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Author to whom correspondence should be addressed.
Cells 2019, 8(3), 209; https://doi.org/10.3390/cells8030209
Received: 1 February 2019 / Revised: 26 February 2019 / Accepted: 27 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Proteostasis and Autophagy)
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Abstract

The presenilin (PS) proteins exert a crucial role in the pathogenesis of Alzheimer disease (AD) by mediating the intramembranous cleavage of amyloid precursor protein (APP) and the generation of amyloid β-protein (Aβ). The two homologous proteins PS1 and PS2 represent the catalytic subunits of distinct γ-secretase complexes that mediate a variety of cellular processes, including membrane protein metabolism, signal transduction, and cell differentiation. While the intramembrane cleavage of select proteins by γ-secretase is critical in the regulation of intracellular signaling pathways, the plethora of identified protein substrates could also indicate an important role of these enzyme complexes in membrane protein homeostasis. In line with this notion, PS proteins and/or γ-secretase has also been implicated in autophagy, a fundamental process for the maintenance of cellular functions and homeostasis. Dysfunction in the clearance of proteins in the lysosome and during autophagy has been shown to contribute to neurodegeneration. This review summarizes the recent knowledge about the role of PS proteins and γ-secretase in membrane protein metabolism and trafficking, and the functional relation to lysosomal activity and autophagy. View Full-Text
Keywords: presenilin; γ-secretase; autophagy; Alzheimer disease; proteostasis; intramembrane proteolysis; membrane trafficking presenilin; γ-secretase; autophagy; Alzheimer disease; proteostasis; intramembrane proteolysis; membrane trafficking
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Oikawa, N.; Walter, J. Presenilins and γ-Secretase in Membrane Proteostasis. Cells 2019, 8, 209.

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