Presenilins: how much more than γ-secretase?!

Abstract:

: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) Ca(2+) 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.

journal_name

Biochem Soc Trans

authors

Coen K,Annaert W

doi

10.1042/BST0381474

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

1474-8

issue

6

eissn

0300-5127

issn

1470-8752

pii

BST0381474

journal_volume

38

pub_type

杂志文章
  • A model for the aberrant DNA methylomes in aging cells and cancer cells.

    abstract::DNA methylation at the fifth position of cytosine is a major epigenetic mark conserved in plants and mammals. Genome-wide DNA methylation patterns are dynamically controlled by integrated activities of establishment, maintenance, and removal. In both plants and mammals, a pattern of global DNA hypomethylation coupled ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180218

    authors: Zhang H,Zhang K,Zhu JK

    更新日期:2019-08-30 00:00:00

  • Innate link between NF-kappaB activity and ubiquitin-like modifiers.

    abstract::Among the several signalling pathways regulated by ubiquitin and ubiquitin-like proteins, the one activating NF-kappaB (nuclear factor kappaB) is certainly one of the best characterized. The regulation of the activity of this transcription factor by members of the ubiquitin family occurs at various levels, imposing ov...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0360853

    authors: Lang V,Rodríguez MS

    更新日期:2008-10-01 00:00:00

  • The complex matter of DNA double-strand break detection.

    abstract::To maintain genomic stability, despite constant exposure to agents that damage DNA, eukaryotic cells have developed elaborate and highly conserved pathways of DNA damage sensing, signalling and repair. In this review, we concentrate mainly on what we know about DNA damage sensing with particular reference to Lcd1p, a ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310040

    authors: Bradbury JM,Jackson SP

    更新日期:2003-02-01 00:00:00

  • Green oxidations with laccase-mediator systems.

    abstract::Laccases are oxidase enzymes produced by 'white rot' fungi as part of a complex armoury of redox enzymes used to break down lignin--part of the carbon cycle of nature. Laccases alone or in combination with redox co-catalysts have been shown to oxidize xenobiotic compounds under conditions that can be described as 'gre...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20060304

    authors: Wells A,Teria M,Eve T

    更新日期:2006-04-01 00:00:00

  • Chemically targeting the PI3K family.

    abstract::PI3K (phosphoinositide 3-kinase) is a key regulator of cell growth, metabolism and survival. The frequent activation of the PI3K pathway in cancer has stimulated widespread interest in identifying potent and selective inhibitors of PI3K isoforms. The present paper highlights recent progress in identifying such molecul...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0350245

    authors: Knight ZA,Shokat KM

    更新日期:2007-04-01 00:00:00

  • Polyamine biosynthetic enzymes as drug targets in parasitic protozoa.

    abstract::Molecular, biochemical and genetic characterization of ornithine decarboxylase, S -adenosylmethionine decarboxylase and spermidine synthase establishes that these polyamine-biosynthetic enzymes are essential for growth and survival of the agents that cause African sleeping sickness, Chagas' disease, leishmaniasis and ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310415

    authors: Heby O,Roberts SC,Ullman B

    更新日期:2003-04-01 00:00:00

  • Cell respiration and formation of reactive oxygen species: facts and artefacts.

    abstract::It is generally taken as an established fact that mitochondrial respiration is associated with the generation of small amounts of ROS (reactive oxygen species). There are many arguments supporting this side activity. A major argument is the particular physico-chemical configuration of dioxygen, which prevents the tran...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0311308

    authors: Nohl H,Kozlov AV,Gille L,Staniek K

    更新日期:2003-12-01 00:00:00

  • Studies of focal adhesion assembly.

    abstract::Recent studies of some proteins involved in the formation of focal adhesions are described. These include fibronectin, integrins, talin, Dok1 and filamin. Emphasis is placed on features that facilitate regulated assembly of complexes; these include a modular construction and flexible regions that provide interaction s...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0360263

    authors: Campbell ID

    更新日期:2008-04-01 00:00:00

  • Cytoplasmic tail of IL-13Ralpha2 regulates IL-4 signal transduction.

    abstract::IL (interleukin)-4 and IL-13 are key cytokines in the pathogenesis of allergic inflammatory disease. IL-4 and IL-13 share many functional properties as a result of their utilization of a common receptor complex comprising IL-13Ralpha1 (IL-13 receptor alpha-chain 1) and IL-4Ralpha. The second IL-13R (IL-13 receptor) ha...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370873

    authors: Andrews AL,Nordgren IK,Kirby I,Holloway JW,Holgate ST,Davies DE,Tavassoli A

    更新日期:2009-08-01 00:00:00

  • Phosphorylation of Zn(II)2Cys6 proteins: a cause or effect of transcriptional activation?

    abstract::Many Zn(II)2Cys6 transcriptional regulators exhibit changes in phosphorylation that are coincident with their roles in transcriptional activation. It is, however, unclear whether these changes occur as a cause of, or as a result of, transcriptional activation. In this paper, we explore the relationship between these t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0340794

    authors: Leverentz MK,Reece RJ

    更新日期:2006-11-01 00:00:00

  • Current understanding of plant Polycomb group proteins and the repressive histone H3 Lysine 27 trimethylation.

    abstract::Polycomb group (PcG) proteins are highly conserved chromatin-modifying complexes that implement gene silencing in higher eukaryotes. Thousands of genes and multiple developmental processes are regulated by PcG proteins. As the first chromatin modifier been identified in model plant Arabidopsis thaliana, the methyltran...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20200192

    authors: Jiao H,Xie Y,Li Z

    更新日期:2020-08-28 00:00:00

  • Gene expression regulation by heat-shock proteins: the cardinal roles of HSF1 and Hsp90.

    abstract::The ability to permit gene expression is managed by a set of relatively well known regulatory mechanisms. Nonetheless, this property can also be acquired during a life span as a consequence of environmental stimuli. Interestingly, some acquired information can be passed to the next generation of individuals without mo...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20170335

    authors: Mazaira GI,Daneri-Becerra C,Zgajnar NR,Lotufo CM,Galigniana MD

    更新日期:2018-02-19 00:00:00

  • The use of in situ haemoglobin-free perfused liver in metabolic-control analysis.

    abstract::In this study the network of ATP-consuming and -producing reactions, interacting via the cytosolic ATP/ADP+P(i) system, was studied for the first time in an intact organ, the isolated perfused rat liver, using top-down metabolic-control analysis. Flux control in the metabolically resting state (only oxidative phosphor...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0280109

    authors: Soboll S,Brown GC

    更新日期:2000-02-01 00:00:00

  • Control of growth factor receptor dynamics by reversible ubiquitination.

    abstract::Activated tyrosine kinase receptors acquire ubiquitin tags. Ubiquitination governs receptor down-regulation through interaction with components of the endosomal ESCRT (endosomal sorting complexes required for transport) machinery that shepherds receptors into luminal vesicles of multivesicular bodies en route to the l...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0340754

    authors: Urbé S,McCullough J,Row P,Prior IA,Welchman R,Clague MJ

    更新日期:2006-11-01 00:00:00

  • Model-based evolutionary analysis: the natural history of phage-shock stress response.

    abstract::The evolution of proteins is inseparably linked to their function. Because most biological processes involve a number of different proteins, it may become impossible to study the evolutionary properties of proteins in isolation. In the present article, we show how simple mechanistic models of biological processes can ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0370762

    authors: Huvet M,Toni T,Tan H,Jovanovic G,Engl C,Buck M,Stumpf MP

    更新日期:2009-08-01 00:00:00

  • Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis.

    abstract::Targeting of estrogen receptor is commonly used as a first-line treatment for hormone-positive breast cancer patients, and is considered as a keystone of systemic cancer therapy. Likewise, HER2-targeted therapy significantly improved the survival of HER2-positive breast cancer patients, indicating that targeted therap...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20191055

    authors: Lev S

    更新日期:2020-04-29 00:00:00

  • Probing the druggability of protein-protein interactions: targeting the Notch1 receptor ankyrin domain using a fragment-based approach.

    abstract::In order to achieve greater selectivity in drug discovery, researchers in both academia and industry are targeting cell regulatory systems. This often involves targeting the protein-protein interactions of regulatory multiprotein assemblies. Protein-protein interfaces are widely recognized to be challenging targets as...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0391327

    authors: Abdel-Rahman N,Martinez-Arias A,Blundell TL

    更新日期:2011-10-01 00:00:00

  • A study of the horseradish peroxidase catalytic site by FTIR spectroscopy.

    abstract::Vibrational changes in the catalytic site of horseradish peroxidase were investigated by FTIR (Fourier-transform infrared) spectroscopy in the 1000-2500 cm(-1) range. Difference spectra were generated by photolysis of the haemII-CO compound at different pH/pD values. The spectra report on the fine structure around the...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330886

    authors: Ingledew WJ,Rich PR

    更新日期:2005-08-01 00:00:00

  • New insights into the evolutionary conservation of the sole PIKK pseudokinase Tra1/TRRAP.

    abstract::Phosphorylation by protein kinases is a fundamental mechanism of signal transduction. Many kinase families contain one or several members that, although evolutionarily conserved, lack the residues required for catalytic activity. Studies combining structural, biochemical, and functional approaches revealed that these ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180496

    authors: Elías-Villalobos A,Fort P,Helmlinger D

    更新日期:2019-12-20 00:00:00

  • The petite purple photosynthetic powerpack.

    abstract::Photoreaction centres are Nature's solar batteries. These nanometre-scale power producers are responsible for transducing the energy of sunlight into a form that can be used by biological systems, thereby powering most of the biological activity on the planet. Although to the layman the word 'photosynthesis' is usuall...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370400

    authors: Jones MR

    更新日期:2009-04-01 00:00:00

  • Mass spectrometry approaches for vitamin E research.

    abstract::Vitamin E is an important nutrient with antioxidant and non-antioxidant functions, and certain evidence suggests that it has a cardiovascular protective role. It is therefore important to maintain an optimal vitamin E status. In the present paper, a number of MS applications to monitor vitamin E status and its interac...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0361066

    authors: Lodge JK

    更新日期:2008-10-01 00:00:00

  • Heterodimers and family-B GPCRs: RAMPs, CGRP and adrenomedullin.

    abstract::RAMPs (receptor activity-modifying proteins) are single-pass transmembrane proteins that associate with certain family-B GPCRs (G-protein-coupled receptors). Specifically for the CT (calcitonin) receptor-like receptor and the CT receptor, this results in profound changes in ligand binding and receptor pharmacology, al...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320843

    authors: Conner AC,Simms J,Hay DL,Mahmoud K,Howitt SG,Wheatley M,Poyner DR

    更新日期:2004-11-01 00:00:00

  • Expanding and understanding the genetic toolbox of the hyperthermophilic genus Sulfolobus.

    abstract::Although Sulfolobus species are among the best studied archaeal micro-organisms, the development and availability of genetic tools has lagged behind. In the present paper, we discuss the latest progress in understanding recombination events of exogenous DNA into the chromosomes of Sulfolobus solfataricus and Sulfolobu...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0370097

    authors: Wagner M,Berkner S,Ajon M,Driessen AJ,Lipps G,Albers SV

    更新日期:2009-02-01 00:00:00

  • Opportunities for bioprocess monitoring using FRET biosensors.

    abstract::Bioprocess monitoring is used to track the progress of a cell culture and ensure that the product quality is maintained. Current schemes for monitoring metabolism rely on offline measurements of samples of the extracellular medium. However, in the era of synthetic biology, it is now possible to design and implement bi...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20130103

    authors: Constantinou A,Polizzi KM

    更新日期:2013-10-01 00:00:00

  • Floral stem cells: from dynamic balance towards termination.

    abstract::During early flower development in Arabidopsis, floral stem cells proliferate and produce a sufficient amount of cells that are recruited for organogenesis. However, after the central organ primordia initiate, stem cell activity in the floral meristem is terminated to ensure the differentiation of a fixed number of fl...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380613

    authors: Sun B,Ito T

    更新日期:2010-04-01 00:00:00

  • Cell-free synthetic biology for in vitro prototype engineering.

    abstract::Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20170011

    authors: Moore SJ,MacDonald JT,Freemont PS

    更新日期:2017-06-15 00:00:00

  • Self-assembly in the carboxysome: a viral capsid-like protein shell in bacterial cells.

    abstract::Many proteins self-assemble to form large supramolecular complexes. Numerous examples of these structures have been characterized, ranging from spherical viruses to tubular protein assemblies. Some new kinds of supramolecular structures are just coming to light, while it is likely there are others that have not yet be...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350508

    authors: Yeates TO,Tsai Y,Tanaka S,Sawaya MR,Kerfeld CA

    更新日期:2007-06-01 00:00:00

  • A-kinase-anchoring proteins and cytoskeletal signalling events.

    abstract::Targeting of protein kinases and phosphatases to the cytoskeleton enhances the regulation of many signalling events. Cytoskeletal signalling complexes facilitate this process by optimizing the relay of messages from membrane receptors to specific sites on the actin cytoskeleton. These signals influence fundamental cel...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310087

    authors: Scott JD

    更新日期:2003-02-01 00:00:00

  • The ESCRT machinery: new functions in viral and cellular biology.

    abstract::The ESCRT (endosomal sorting complex required for transport) machinery consists of a number of cytosolic proteins that make up three functional subcomplexes: ESCRT-I, ESCRT-II and ESCRT-III. These proteins function in multivesicular body formation and cell division and are co-opted by enveloped retroviruses to facilit...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370195

    authors: Carlton JG,Martin-Serrano J

    更新日期:2009-02-01 00:00:00

  • Ion translocation by the Escherichia coli NADH:ubiquinone oxidoreductase (complex I).

    abstract::The energy-converting NADH:ubiquinone oxidoreductase, also known as respiratory complex I, couples the transfer of electrons from NADH to ubiquinone with the translocation of ions across the membrane. It was assumed that the complex exclusively works as a proton pump. Recently, it has been proposed that complex I from...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330836

    authors: Friedrich T,Stolpe S,Schneider D,Barquera B,Hellwig P

    更新日期:2005-08-01 00:00:00