Abstract:
:The competitive ectodomain shedding of amyloid-β precursor protein (APP) by α-secretase and β-secretase, and the subsequent regulated intramembrane proteolysis by γ-secretase are the key processes in amyloid-β peptides (Aβ) generation. Previous studies indicate that secretases form binary complex and the interactions between secretases take part in substrates processing. However, whether α-, β- and γ-secretase could form ternary complex remains to be explored. Here, we adopted bimolecular fluorescence complementation in combination with fluorescence resonance energy transfer (BiFC-FRET) to visualize the formation of triple secretase complex. We show that the interaction between α-secretase ADAM10 and β-secretase BACE1 could be monitored by BiFC assay and the binding of APP to α-/β-secretase binary complex was revealed by BiFC-FRET. Further, we observed that γ-secretase interacts with α-/β-secretase binary complex, providing evidence that α-, β- and γ-secretase might form a ternary complex. Thus our study extends the interplay among Alzheimer's disease (AD) related α-/β-/γ-secretase.
journal_name
Front Mol Neuroscijournal_title
Frontiers in molecular neuroscienceauthors
Wang X,Pei Gdoi
10.3389/fnmol.2018.00431subject
Has Abstractpub_date
2018-11-27 00:00:00pages
431issn
1662-5099journal_volume
11pub_type
杂志文章abstract::Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great po...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00030
更新日期:2017-02-07 00:00:00
abstract::Autism spectrum disorders (ASD) have a higher prevalence in male individuals compared to females, with a ratio of affected boys compared to girls of 4:1 for ASD and 11:1 for Asperger syndrome. Mutations in the SHANK genes (comprising SHANK1, SHANK2 and SHANK3) coding for postsynaptic scaffolding proteins have been tig...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00337
更新日期:2018-09-25 00:00:00
abstract::Among all organs of an adult animal, the central nervous system stands out because of its vast complexity and morphological diversity. During early development, the entire central nervous system develops from an apparently homogenous group of progenitors that differentiate into all neural cell types. Therefore, unders...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2019.00140
更新日期:2019-05-31 00:00:00
abstract::Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neu...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2013.00050
更新日期:2013-12-17 00:00:00
abstract::The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00055
更新日期:2017-03-02 00:00:00
abstract::Kainate (KA) is a potent neurotoxin that has been widely used experimentally to induce acute brain seizures and, after repetitive treatments, as a chronic model of temporal lobe epilepsy (TLE), with similar features to those observed in human patients with TLE. However, whether KA activates KA receptors (KARs) as an a...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2018.00217
更新日期:2018-06-22 00:00:00
abstract::The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00008
更新日期:2017-01-23 00:00:00
abstract::Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00319
更新日期:2017-10-06 00:00:00
abstract::The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including polycomb repressive complex 2 (PRC2). EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00076
更新日期:2019-04-09 00:00:00
abstract::Age-progressive neurodegenerative pathologies, including Alzheimer's disease (AD), are distinguished and diagnosed by disease-specific components of intra- or extra-cellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, and is involved in the etiology of neurological dis...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00310
更新日期:2019-12-12 00:00:00
abstract::Itch, a sensation eliciting a desire to scratch, is distinct from but not completely independent of pain. Inspiring achievements have been made in the characterization of itch-related receptors and neurotransmitters, but the molecular mechanisms controlling the development of pruriceptors remain poorly understood. Her...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00205
更新日期:2017-06-28 00:00:00
abstract::Spinal muscular atrophy (SMA) is a severe neurodegenerative disorder that occurs in early childhood. The disease is caused by the deletion/mutation of the survival motor neuron 1 (SMN1) gene resulting in progressive skeletal muscle atrophy and paralysis, due to the degeneration of spinal motor neurons (MNs). Currently...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00308
更新日期:2018-09-04 00:00:00
abstract::Connexin channels play numerous essential roles in virtually every organ by mediating solute exchange between adjacent cells, or between cytoplasm and extracellular milieu. Our understanding of the structure-function relationship of connexin channels relies on X-ray crystallographic data for human connexin 26 (hCx26) ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00170
更新日期:2018-05-31 00:00:00
abstract::Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00179
更新日期:2018-05-29 00:00:00
abstract::Epilepsy is a chronic brain dysfunction induced by an abnormal neuronal discharge that is caused by complicated psychopathologies. Recently, accumulating studies have revealed a close relationship between inflammation and epilepsy. Specifically, microglia and astrocytes are important inflammatory cells in the central ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2020.554547
更新日期:2020-09-04 00:00:00
abstract::Membrane bound guanylate cyclases are expressed in rod and cone cells of the vertebrate retina and mutations in several domains of rod outer segment guanylate cyclase 1 (ROS-GC1 encoded by the gene GUCY2D) correlate with different forms of retinal degenerations. In the present work we investigated the biochemical cons...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2014.00004
更新日期:2014-02-26 00:00:00
abstract::Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer's Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane gl...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2016.00130
更新日期:2016-11-25 00:00:00
abstract::This review will consider the impact of compromised PTEN signaling in brain patterning. We approach understanding the contribution of PTEN to nervous system development by surveying the findings from the numerous genetic loss-of-function models that have been generated as well as other forms of PTEN inactivation. By e...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2014.00035
更新日期:2014-05-14 00:00:00
abstract::Many genes controlling neuronal development also regulate adult neurogenesis. We investigated in vivo the effect of Sonic hedgehog (Shh) signaling activation on patterning and neurogenesis of the hippocampus and behavior of Patched1 (Ptch1) heterozygous mice (Ptch1+/- ). We demonstrated for the first time, that Ptch1+...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00168
更新日期:2018-05-23 00:00:00
abstract::Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is a neurodegenerative disorder caused by loss-of-function mutations in the cystatin B (CSTB) gene. Progression of the clinical symptoms in EPM1 patients, including stimulus-sensitive myoclonus, tonic-clonic seizures, and ataxia, are well described. How...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.570640
更新日期:2020-11-13 00:00:00
abstract::Membrane fusion is one of the most fundamental physiological processes in eukaryotes for triggering the fusion of lipid and content, as well as the neurotransmission. However, the architecture features of neurotransmitter release machinery and interdependent mechanism of synaptic membrane fusion have not been extensiv...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00168
更新日期:2017-06-07 00:00:00
abstract::The anterior cingulate cortex (ACC) is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2017.00289
更新日期:2017-09-12 00:00:00
abstract::The importance of catecholamines in post-traumatic stress disorder (PTSD) still needs to be explored. We aimed to evaluate epinephrine's (EPI) causal role and molecular mechanism for the persistence of PTSD traumatic memories. Wild-type (WT) and EPI-deficient mice (phenylethanolamine-N-methyltransferase-knockout mice,...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.588802
更新日期:2020-10-26 00:00:00
abstract::Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnmol.2017.00167
更新日期:2017-06-06 00:00:00
abstract::Alzheimer's disease (AD) is a widely distributed neurodegenerative disease characterized clinically by cognitive deficits and pathologically by formation of amyloid-β (Aβ) plaque and neurofibrillary tangles (NFTs) in the brain. Vanadium is a biological trace element that has a function to mimic insulin for diabetes. B...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00021
更新日期:2020-03-10 00:00:00
abstract::Collateral sprouting of surviving axons contributes to the synaptic reorganization after brain injury. To study this clinically relevant phenomenon, we used complex organotypic tissue cultures of mouse entorhinal cortex (EC) and hippocampus (H). Single EC-H cultures were generated to analyze associational sprouting, a...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00270
更新日期:2019-11-12 00:00:00
abstract::Alzheimer's disease (AD) pathology is characterized by the aggregation of beta-amyloid (Aβ) and tau in the form of amyloid plaques and neurofibrillary tangles in the brain. It has been found that a synergistic relationship between these two proteins may contribute to their roles in disease progression. However, how Aβ...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00268
更新日期:2019-11-08 00:00:00
abstract::Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These mutations result in the complete absence or truncated expression of the laminin-α2 chain. The α2-chain is a major component of the laminin-211 and laminin-221 isoforms, the p...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2020.00001
更新日期:2020-02-11 00:00:00
abstract::ADP-ribosylation of the P2X7k splice variant on mouse T cells by Ecto-ADP-ribosyltransferase ARTC2.2 in response to its substrate extracellular nicotinamide adenine dinucleotide (NAD+) triggers cell death. Since NAD+ is released as a danger signal during tissue damage, this NAD+-induced cell death (NICD) may impact th...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2019.00330
更新日期:2020-01-14 00:00:00
abstract::N-methyl-D-aspartate receptors (NMDARs) play critical roles in both excitatory neurotransmission and synaptic plasticity. NMDARs containing the nonconventional GluN3A subunit have different functional properties compared to receptors comprised of GluN1/GluN2 subunits. Previous studies showed that GluN1/GluN2 receptors...
journal_title:Frontiers in molecular neuroscience
pub_type: 杂志文章
doi:10.3389/fnmol.2018.00188
更新日期:2018-06-04 00:00:00