AD (Alzheimer's disease) is a neurodegenerative disease characterized by a gradual loss of neurons and the accumulation of neurotoxic Aβ (amyloid β-peptide) and hyperphosphorylated tau. The discovery of mutations in three genes, PSEN1 (presenilin 1), PSEN2 (presenilin 2) and APP (amyloid precursor protein), in patients with FAD (familial AD) has made an important contribution towards an understanding of the disease aetiology; however, a complete molecular mechanism is still lacking. Both presenilins belong to the γ-secretase complex, and serve as the catalytic entity needed for the final cleavage of APP into Aβ. PSEN only functions within the γ-secretase complex through intra- and inter-molecular interactions with three other membrane components, including nicastrin, Aph-1 (anterior pharynx defective-1) and Pen-2 (PSEN enhancer-2). However, although the list of γ-secretase substrates is still expanding, other non-catalytic activities of presenilins are also increasing the complexity behind its molecular contribution towards AD. These γ-secretase-independent roles are so far mainly attributed to PSEN1, including the transport of membrane proteins, cell adhesion, ER (endoplasmic reticulum) Ca2+ regulation and cell signalling. In the present minireview, we discuss the current understanding of the γ-secretase-independent roles of PSENs and their possible implications in respect of AD.
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Conference Article|
November 24 2010
Presenilins: how much more than γ-secretase?!
Katrijn Coen;
Katrijn Coen
1
1Membrane Trafficking Laboratory, Department for Molecular and Developmental Genetics, VIB, Leuven, Belgium, and Membrane Trafficking Laboratory, Department of Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium
1To whom correspondence should be addressed (email Wim.Annaert@cme.vib-kuleuven.be)
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Wim Annaert
Wim Annaert
1Membrane Trafficking Laboratory, Department for Molecular and Developmental Genetics, VIB, Leuven, Belgium, and Membrane Trafficking Laboratory, Department of Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium
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Publisher: Portland Press Ltd
Received:
May 12 2010
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem Soc Trans (2010) 38 (6): 1474–1478.
Article history
Received:
May 12 2010
Citation
Katrijn Coen, Wim Annaert; Presenilins: how much more than γ-secretase?!. Biochem Soc Trans 1 December 2010; 38 (6): 1474–1478. doi: https://doi.org/10.1042/BST0381474
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