Affinage

ACHE

Acetylcholinesterase · UniProt P22303

Length
614 aa
Mass
67.8 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ACHE encodes acetylcholinesterase, a hydrolase whose pre-mRNA undergoes 3′ alternative splicing to generate isoforms (AChE-T/S, AChE-R, AChE-H) that share an identical catalytic domain but carry distinct C-termini dictating their multimeric assembly, membrane association, and non-hydrolytic protein partnerships (PMID:16516310). Tissue-specific deletion of exon 5 versus exon 6 in mice established that the exon-5 splice yields the GPI-anchored hematopoietic form while the exon-6 splice produces the form binding PRiMA/ColQ in brain and muscle, and an intronic enhancer drives muscle-specific expression (PMID:16289062). At the neuromuscular junction, expression of these synaptic species is controlled by nerve-derived CGRP through a PKA-dependent cascade and by nerve-evoked electrical activity, which coordinate assembly of ColQ-anchored asymmetric and PRiMA-anchored globular forms (PMID:10757523, PMID:18514177); AChE itself acts as a downstream effector required for NMJ integrity in a TDP-43 ALS model (PMID:33499374). Beyond catalysis, the stress-induced readthrough variant AChE-R forms a complex with the scaffold RACK1 and PKCε to drive proliferation under CREB suppression and partners with enolase to raise cellular ATP (PMID:15153340, PMID:18572152), while its C-terminal peptide triggers RIPK1/MLKL-dependent necroptosis in ovarian granulosa cells (PMID:25766324). AChE functions broadly as a pro-apoptotic factor: it accumulates in the nucleus of dying cells, and its genetic loss or pharmacological inhibition reduces caspase activation, p53 induction, and the Bax/Bcl-2 ratio in vivo (PMID:11985878, PMID:20054652). In neurodegeneration, AChE promotes amyloid fibril assembly into toxic AChE–Aβ complexes that deplete β-catenin and impair Wnt signaling (PMID:15975054), and its own expression is suppressed by the copper-binding E1 domain of APP and by miR-124/miR-132 targeting (PMID:27062894, PMID:28209997, PMID:27977009), the latter positioning AChE as a regulator of the cholinergic anti-inflammatory pathway (PMID:27977009). The His322Asn substitution defines the YT blood group polymorphism on red blood cells (PMID:8488842).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1993 High

    Established the molecular basis of a human blood group antigen by mapping it to ACHE, showing the gene product is displayed on red cells.

    Evidence DNA sequencing of ACHE from donors of known YT phenotype, correlating His322Asn with Yta/Ytb

    PMID:8488842

    Open questions at the time
    • Does not address whether the substitution alters catalytic activity or membrane anchoring
    • No structural explanation for antigenicity
  2. 2000 Medium

    Defined the signaling pathway by which motor nerve input drives synaptic AChE expression in muscle, answering how innervation controls enzyme levels.

    Evidence PKA activity assays, constitutively active Gαs/Gαi transfection, and PKA inhibitors in chick myotubes

    PMID:10757523

    Open questions at the time
    • Downstream transcription factors not identified
    • Chick system; human relevance not directly tested
  3. 2002 Medium

    First implicated AChE in apoptosis as a non-catalytic role, showing its induction and nuclear aggregation are required for neuronal cell death.

    Evidence Antisense knockdown, subcellular fractionation/imaging, and caspase-3 assay in SK-N-SH cells

    PMID:11985878

    Open questions at the time
    • Nuclear targets of AChE not identified
    • Isoform responsible not resolved
  4. 2004 Medium

    Identified a proliferative signaling function for the stress-induced AChE-R variant through a defined scaffold/kinase complex, distinguishing isoform-specific non-hydrolytic activity.

    Evidence Co-IP, PKC phosphorylation and BrdU assays, antisense knockdown in U87MG glioblastoma cells

    PMID:15153340

    Open questions at the time
    • Single cell line
    • Mechanism by which CREB suppresses the effect not fully resolved
  5. 2004 Medium

    Linked AChE to Alzheimer pathology mechanistically by showing it accelerates Aβ fibril assembly and impairs neuroprotective Wnt/β-catenin signaling.

    Evidence In vitro fibril assays, hippocampal neuron culture, in vivo rat injection, β-catenin quantification and Wnt-3a rescue

    PMID:15975054

    Open questions at the time
    • Whether catalytic activity is required for fibril promotion not established
    • Direct AChE–β-catenin link not defined
  6. 2005 High

    Resolved the genetic architecture of isoform-specific anchoring and tissue-specific transcription via targeted deletion of individual exons and a regulatory element.

    Evidence Homologous recombination and Cre/loxP deletion of exons 5/6 and intronic enhancer in mice, with tissue activity assays

    PMID:16289062

    Open questions at the time
    • Trans-acting factors binding the muscle enhancer not identified
    • Functional consequences of GPI vs PRiMA anchoring in vivo not detailed here
  7. 2006 High

    Consolidated the model that 3′ splicing generates catalytically identical but functionally distinct AChE isoforms differentially induced by stress.

    Evidence Splice variant and multimeric form characterization reviewing biochemical literature

    PMID:16516310

    Open questions at the time
    • Review consolidation rather than new primary data
    • Quantitative tissue distribution of variants not the focus
  8. 2008 Medium

    Expanded the non-hydrolytic interactome of AChE-R to glycolytic and apoptotic machinery, linking the isoform to cellular energetics and chemoresistance.

    Evidence Yeast two-hybrid, Co-IP, in vitro enolase assay, ATP measurement and siRNA in CHO cells

    PMID:18572152

    Open questions at the time
    • Modest (12%/25%) effect sizes
    • p73 competition not validated in disease models
  9. 2008 Medium

    Distinguished the signaling cascades by which CGRP and electrical activity separately control AChE catalytic subunit and anchoring partner expression at the NMJ.

    Evidence Muscle innervation/denervation, signaling inhibition, subunit mRNA/protein analysis

    PMID:18514177

    Open questions at the time
    • Specific transcription factor targets not mapped
    • Largely synthesis of one lab's data
  10. 2009 Medium

    Mapped the pro-apoptotic interactions of an N-terminally extended AChE-S variant to death-pathway kinases and FAS, with an in vivo lethality readout.

    Evidence Peptide array, Co-IP validation, and microinjection into mouse oocytes

    PMID:19533292

    Open questions at the time
    • Physiological abundance of N-AChE-S unclear
    • Direct causal interaction driving lethality not isolated
  11. 2010 High

    Provided genetic and pharmacological in vivo proof that AChE is a pro-apoptotic factor operating through the p53/Bax axis.

    Evidence AChE-knockout mice plus inhibitors in renal ischemia/reperfusion, with caspase, p53, Bax/Bcl-2 readouts

    PMID:20054652

    Open questions at the time
    • Which AChE isoform mediates apoptosis not specified
    • Mechanism linking AChE to p53 phosphorylation undefined
  12. 2015 Medium

    Demonstrated a caspase-independent death mode driven by the AChE-R C-terminal peptide, extending AChE non-hydrolytic signaling to necroptosis in reproductive tissue.

    Evidence Follicular fluid enzymatic assay, IHC, ARP peptide treatment with RIPK1/MLKL inhibitors and LDH assay in granulosa cells

    PMID:25766324

    Open questions at the time
    • Endogenous ARP generation in vivo not shown
    • Receptor coupling ARP to RIPK1 not identified
  13. 2015 Medium

    Showed engineered AChE retains catalysis and organophosphate reactivity with greatly extended circulation, establishing utility as a bioscavenger scaffold.

    Evidence Recombinant AChE-Fc enzymatic and ligand-binding assays, OP reactivity, and mouse pharmacokinetics

    PMID:26121420

    Open questions at the time
    • Protective efficacy against OP poisoning not tested
    • Not a finding about endogenous gene function
  14. 2016 Medium

    Identified APP as an upstream repressor of AChE expression acting through its copper-binding E1 domain independent of APP processing.

    Evidence APP overexpression/siRNA, RT-PCR, Western, domain-deletion constructs and metalloproteinase inhibitors in neuronal cells

    PMID:27062894

    Open questions at the time
    • Transcriptional intermediary linking E1 domain to ACHE not identified
    • Single neuronal model
  15. 2016 Medium

    Placed AChE within the cholinergic anti-inflammatory pathway by showing miR-124 directly suppresses it to restrain macrophage cytokine output.

    Evidence miR-124 overexpression, 3′-UTR targeting, cytokine ELISA and AChE inhibitor treatment in intestinal macrophages

    PMID:27977009

    Open questions at the time
    • Relative contribution of AChE vs STAT3 targeting not separated
    • In vivo inflammation model not used
  16. 2017 Medium

    Defined isoform-selective post-transcriptional control by showing miR-132 preferentially binds AChE-R, enabling re-balancing of neurotransmission.

    Evidence Surface plasmon resonance binding and AM132 antisense treatment in mice with cortical miRNA-seq

    PMID:28209997

    Open questions at the time
    • Structural basis of isoform selectivity unresolved
    • Functional behavioral consequences not detailed
  17. 2021 Medium

    Positioned AChE as a downstream effector of TDP-43 required for NMJ assembly, connecting it to ALS pathophysiology.

    Evidence Zebrafish tdp-43 morpholino knockdown with human AChE rescue, NMJ immunostaining and motor assays

    PMID:33499374

    Open questions at the time
    • Whether catalytic or structural AChE function mediates rescue not resolved
    • Direct TDP-43 regulation of ache transcription not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the catalytically identical isoforms partition between hydrolytic and non-hydrolytic (apoptotic, necroptotic, proliferative) signaling roles in a given cell, and what the immediate molecular targets of nuclear AChE are, remains unresolved.
  • No unifying mechanism linking AChE to p53/Bax or RIPK1/MLKL
  • Nuclear substrates/partners of pro-apoptotic AChE unidentified
  • Determinants of isoform-specific function in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005886 plasma membrane 2 GO:0005576 extracellular region 1 GO:0005634 nucleus 1
Pathway
R-HSA-5357801 Programmed Cell Death 3 R-HSA-112316 Neuronal System 2 R-HSA-168256 Immune System 1
Partners
COLQENOLASEFASGSK3P73PKCΕPRIMARACK1
Complex memberships
AChE-R/RACK1/PKCε complexColQ-anchored asymmetric AChEPRiMA-anchored globular AChE

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 A single nucleotide mutation at codon 322 in the human ACHE gene (His322→Asn322, CAC→AAC) accounts for the YT blood group polymorphism: the wild-type His322 form is the YT1 (Yta) antigen and the variant Asn322 form is the YT2 (Ytb) antigen, establishing acetylcholinesterase as the YT blood group antigen on red blood cells. DNA sequencing of human ACHE gene from donors of known YT phenotype American journal of human genetics High 8488842
2006 AChE pre-mRNA undergoes 3′ alternative splicing to produce variant proteins (AChE-T, AChE-R, AChE-H) with identical enzymatic activity but distinct C-termini, leading to different multimeric assemblies, membrane-association patterns, protein partners, and non-hydrolytic functions; the variants are differentially induced under stress. Molecular biology (splice variant characterization), biochemical analysis of multimeric forms, review of experimental literature Trends in neurosciences High 16516310
2004 The stress-induced AChE-R variant forms a triple complex with PKCε and the scaffold protein RACK1 in human U87MG glioblastoma cells, enhances PKCε phosphorylation, and promotes cell proliferation (BrdU incorporation); CREB suppresses this proliferative effect via a PKC-mediated pathway. Co-immunoprecipitation, PKC phosphorylation assay, BrdU incorporation, antisense knockdown, kinase inhibitor experiments Neoplasia (New York, N.Y.) Medium 15153340
2008 The C-terminus of AChE-R (and N-AChE-R) interacts with the glycolytic enzyme enolase and with scaffold protein RACK1 (via yeast two-hybrid and co-immunoprecipitation); the AChE-R C-terminal peptide (ARP) elevates enolase activity by ~12% in vitro, and CHO cells expressing AChE-R (but not AChE-S) show 25% higher ATP levels. AChE-R also competes with RACK1 for interaction with pro-apoptotic p73, modulating the p73 pathway and conferring cis-platinum resistance. Yeast two-hybrid screen, Co-immunoprecipitation, in vitro enolase activity assay, ATP measurement, siRNA knockdown, Western blot Chemico-biological interactions Medium 18572152
2009 The N-terminally extended AChE-S variant (N-AChE-S) promotes apoptosis and interacts with kinases GSK3, Aurora, and GAK, membrane integrin receptors, and the death receptor FAS, as identified by peptide array and validated by co-immunoprecipitation; microinjection of N-AChE-S into mouse oocytes caused embryonic death at the zygotic stage. Microinjection into mouse oocytes, peptide array, co-immunoprecipitation Journal of neural transmission Medium 19533292
2002 AChE expression increases in apoptotic neuroblastoma SK-N-SH cells during long-term culture, with AChE aggregating in the nucleus; suppression of AChE with antisense oligonucleotide rescued cells from apoptosis. Caspase-3 activity was parallel with AChE activation, suggesting AChE plays a pro-apoptotic role in neuronal cells. Antisense oligonucleotide knockdown, immunofluorescence/subcellular fractionation, caspase-3 activity assay Neuroscience research Medium 11985878
2004 AChE increases amyloid fibril assembly forming highly toxic AChE–Aβ complexes; these complexes decrease cytoplasmic β-catenin levels (a key Wnt signaling component) in hippocampal neurons and in vivo, and Wnt-3a activation rescues neuronal survival from Aβ-AChE neurotoxicity. In vitro fibril assembly assay, hippocampal neuron culture, in vivo rat hippocampal injection, β-catenin quantification, Wnt pathway manipulation Current Alzheimer research Medium 15975054
2010 AChE deficiency (AChE-knockout mice) or pharmacological AChE inhibition reduces renal ischemia/reperfusion-induced apoptosis, with decreased caspase-8, -9, -12, and -3 activation, reduced p53 induction and Ser15 phosphorylation, and decreased Bax/Bcl-2 ratio, establishing AChE as a pro-apoptotic factor in vivo. AChE-deficient mouse model, pharmacological inhibition (huperzine A, tacrine, donepezil), caspase activity assays, Western blot (p53, Bax, Bcl-2), histology Apoptosis High 20054652
2015 Enzymatically active AChE is produced by human ovarian granulosa cells and is present in follicular fluid where it hydrolyzes ACh; the readthrough isoform AChE-R is identified in granulosa, theca, and luteal cells. A synthetic AChE-R C-terminal peptide (ARP) induces caspase-independent, RIPK1/MLKL-dependent necroptosis (balloon-like morphology, LDH release) in primary granulosa cells, blocked by necrostatin-1 and necrosulfonamide. Enzymatic activity assay of follicular fluid, immunohistochemistry, ARP peptide treatment of primary cells, RIPK1/MLKL inhibitor experiments, LDH assay, morphological analysis Cell death & disease Medium 25766324
2016 APP overexpression in neuronal cells substantially decreases AChE mRNA, protein, and catalytic activity as well as PRiMA mRNA; siRNA knockdown of APP upregulates AChE mRNA. This regulation does not involve APP processing/AICD but requires the E1 region of APP, specifically its copper-binding domain. AChE shedding from the cell membrane involves a metalloproteinase-mediated mechanism stimulated by cholinergic agonists. APP overexpression and siRNA knockdown, RT-PCR, Western blot, AChE activity assay, domain deletion constructs, metalloproteinase inhibitor experiments Chemico-biological interactions Medium 27062894
2013 AChE-S interacts with the NFκB-activating scaffold protein RACK1 intracellularly, potentially preventing NFκB activation; fluoxetine intercepts LPS-induced decreases in AChE-S, and this is associated with reduced pro-inflammatory cytokine production. The interaction between AChE-S and RACK1/PKCβII was demonstrated by structural modeling and co-immunoprecipitation. Co-immunoprecipitation, ELISA (cytokine measurement), structural modelling, human PBMC experiments Journal of molecular neuroscience Low 24258317
2017 Using surface plasmon resonance, miR-132 preferentially targets the soluble AChE-R isoform over the synaptic AChE-S isoform; peripheral miR-132 blockade by antisense oligonucleotide (AM132) elevated muscle AChE-R 10-fold over AChE-S, re-balancing neurotransmission, and inversely modulated brain immune-related miRNAs. Surface plasmon resonance (SPR), antisense oligonucleotide treatment in mice, cortical miRNA-sequencing, Western blot Scientific reports Medium 28209997
2016 miR-124 directly targets the 3′-UTR of AChE mRNA (and STAT3 mRNA) in intestinal macrophages, suppressing AChE protein expression; overexpression of miR-124 inhibits macrophage activation and reduces IL-6 and TNF-α production, while AChE inhibitors suppress LPS-induced cytokine production, positioning AChE as a negative regulator of the cholinergic anti-inflammatory pathway in intestinal macrophages. miRNA overexpression, 3′-UTR luciferase reporter assay (implied by 'directly target'), Western blot, ELISA (cytokines), AChE inhibitor treatment Cell death & disease Medium 27977009
2000 CGRP-induced AChE expression in chick muscle is mediated by a cAMP-dependent protein kinase (PKA) pathway: CGRP or PKA activators increase intracellular PKA activity ~2-fold, and in vivo transfection of constitutively active Gαs increases AChE mRNA and protein ~2-fold, while constitutively active Gαi has the opposite effect; PKA inhibitors block the induction. PKA activity assay in cultured chick myotubes, in vivo transfection of constitutively active G-protein constructs, Western blot, PKA inhibitor treatment Neuroreport Medium 10757523
2008 Motor nerve-derived CGRP and nerve-evoked electrical activity differentially regulate expression of AChE(T), PRiMA, and ColQ in muscle via distinct downstream signaling cascades, controlling the formation of asymmetric AChE species (A4, A8, A12 with ColQ) and globular G4 AChE (with PRiMA) at the neuromuscular junction. Muscle innervation/denervation experiments, signaling cascade inhibition, gene expression analysis (AChE subunit mRNA and protein), transgenic/transfection approaches Chemico-biological interactions Medium 18514177
2005 Genetic deletion of exon 5 and/or exon 6 of the mouse ACHE gene by homologous recombination demonstrated that exon 5 splice produces the GPI-anchored hematopoietic form, and exon 6 splice produces the form binding PRiMA/ColQ in brain and muscle; deletion of an intronic enhancer region eliminated AChE expression specifically in muscle (while preserving near-normal brain expression), establishing a tissue-specific regulatory element. Homologous recombination in ES cells, Cre/loxP conditional deletion, tissue AChE activity assay, Northern/Western blot Chemico-biological interactions High 16289062
2021 In a zebrafish TDP-43 loss-of-function ALS model, knockdown of tdp-43 decreased ache expression and caused NMJ disassembly and motor deficits; overexpression of human AChE rescued both pre- and post-synaptic NMJ defects, establishing AChE as a downstream effector of TDP-43 required for NMJ integrity. Zebrafish tdp-43 morpholino knockdown, human AChE mRNA overexpression rescue, NMJ immunostaining, motor behavior assay Cells Medium 33499374
2018 Two new allosteric sites in AChE (beyond the known peripheral anionic site) were identified by computational tools; three small-molecule allosteric inhibitors validated by in vitro kinetic assays and molecular dynamics confirmed allosteric inhibition of AChE activity. Computational allosteric site identification, virtual screening, in vitro AChE inhibition assay, kinetic analysis, molecular dynamics simulation Journal of enzyme inhibition and medicinal chemistry Low 29873262
2015 A recombinant AChE–Fc fusion protein (AChE-Fc) retains full enzymatic activity and binding affinity for active-site ligands (BW284c5, propidium) and reacts with organophosphate nerve agents (sarin, VX); when administered to mice, AChE-Fc exhibits markedly prolonged circulatory residence (MRT ~6000 min) compared to other recombinant cholinesterase bioscavengers. Recombinant protein expression, enzymatic activity assay, ligand binding assay, organophosphate reactivity assay, mouse pharmacokinetic study Bioconjugate chemistry Medium 26121420
2005 Polymorphisms in the adjacent PON1 and ACHE genes interact: carriers of distinct compound ACHE/PON1 polymorphisms show genotype-specific differences in plasma AChE and paraoxonase activities; PON1 activity displays inverse association with AChE activity, suggesting cross-regulation between the two loci. Genotyping of 7 polymorphic sites, plasma enzyme activity assays (AChE, BChE, arylesterase, paraoxonase) in 157 individuals, molecular modelling Journal of neurochemistry Low 15715671

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1985 TCGF (IL 2)-receptor inducing factor(s). I. Regulation of IL 2 receptor on a natural killer-like cell line (YT cells). Journal of immunology (Baltimore, Md. : 1950) 397 2578514
2002 Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease. Journal of medicinal chemistry 210 12431053
2006 Virtues and woes of AChE alternative splicing in stress-related neuropathologies. Trends in neurosciences 148 16516310
2019 Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Archiv der Pharmazie 94 31478569
1986 Effect of interleukin 1 on the expression of interleukin 2 receptor (Tac antigen) on human natural killer cells and natural killer-like cell line (YT cells). Journal of immunology (Baltimore, Md. : 1950) 86 3013994
2020 MARK4 Inhibited by AChE Inhibitors, Donepezil and Rivastigmine Tartrate: Insights into Alzheimer's Disease Therapy. Biomolecules 82 32443670
2002 Increased expression of intranuclear AChE involved in apoptosis of SK-N-SH cells. Neuroscience research 80 11985878
2016 Design, Synthesis, and Evaluation of Donepezil-Like Compounds as AChE and BACE-1 Inhibitors. ACS medicinal chemistry letters 74 27190595
1993 Mutation at codon 322 in the human acetylcholinesterase (ACHE) gene accounts for YT blood group polymorphism. American journal of human genetics 69 8488842
2016 Design, synthesis, and AChE inhibitory activity of new benzothiazole-piperazines. Bioorganic & medicinal chemistry letters 66 27789142
2020 Multi-Target Drug Candidates for Multifactorial Alzheimer's Disease: AChE and NMDAR as Molecular Targets. Molecular neurobiology 61 32935230
1993 Functional effects of CD30 on a large granular lymphoma cell line, YT. Inhibition of cytotoxicity, regulation of CD28 and IL-2R, and induction of homotypic aggregation. Journal of immunology (Baltimore, Md. : 1950) 60 8245437
2013 Effect of pharmaceuticals exposure on acetylcholinesterase (AchE) activity and on the expression of AchE gene in the monogonont rotifer, Brachionus koreanus. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 58 24028855
2015 Readthrough acetylcholinesterase (AChE-R) and regulated necrosis: pharmacological targets for the regulation of ovarian functions? Cell death & disease 55 25766324
2004 CREB regulates AChE-R-induced proliferation of human glioblastoma cells. Neoplasia (New York, N.Y.) 53 15153340
2016 AChE and the amyloid precursor protein (APP) - Cross-talk in Alzheimer's disease. Chemico-biological interactions 49 27062894
2000 2B4 stimulation of YT cells induces natural killer cell cytolytic function and invasiveness. Immunology 45 10929061
1992 Detection of Epstein-Barr virus genome in natural-killer-like cell line, YT. Leukemia 45 1313126
2013 Neuronal AChE splice variants and their non-hydrolytic functions: redefining a target of AChE inhibitors? British journal of pharmacology 44 23991627
2020 Triclosan affects motor function in zebrafish larva by inhibiting ache and syn2a genes. Chemosphere 40 33223207
2010 AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion. Apoptosis : an international journal on programmed cell death 40 20054652
2005 Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities. Journal of neurochemistry 38 15715671
2018 Identification of new allosteric sites and modulators of AChE through computational and experimental tools. Journal of enzyme inhibition and medicinal chemistry 37 29873262
2004 Acetylcholinesterase (AChE)--amyloid-beta-peptide complexes in Alzheimer's disease. the Wnt signaling pathway. Current Alzheimer research 34 15975054
2019 Synthesis and AChE Inhibitory Activity of Novel Thiazolylhydrazone Derivatives. Molecules (Basel, Switzerland) 31 31261693
2017 AChE Inhibitors and NMDA Receptor Antagonists in Advanced Alzheimer's Disease. The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists 31 28855009
2007 Oxidative stress and erythrocyte acetylcholinesterase (AChE) in hypertensive and ischemic patients of both acute and chronic stages. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 18031975
1996 CD28-mediated cytotoxicity by the human leukemic NK cell line YT involves tyrosine phosphorylation, activation of phosphatidylinositol 3-kinase, and protein kinase C. Journal of immunology (Baltimore, Md. : 1950) 31 8617944
2022 Anti-Alzheimer's disease potential of traditional chinese medicinal herbs as inhibitors of BACE1 and AChE enzymes. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 36007279
2016 Downregulated expression of microRNA-124 in pediatric intestinal failure patients modulates macrophages activation by inhibiting STAT3 and AChE. Cell death & disease 29 27977009
2008 Inhibition of AChE by malathion and some structurally similar compounds. Journal of enzyme inhibition and medicinal chemistry 29 18608787
2010 Amplification and deletion of the ACHE and BCHE cholinesterase genes in sporadic breast cancer. Cancer genetics and cytogenetics 28 20193849
1994 Carboxypeptidase Taq, a thermostable zinc enzyme, from Thermus aquaticus YT-1: molecular cloning, sequencing, and expression of the encoding gene in Escherichia coli. Bioscience, biotechnology, and biochemistry 28 7765282
2021 Machine learning models for predicting the activity of AChE and BACE1 dual inhibitors for the treatment of Alzheimer's disease. Molecular diversity 27 34327619
2019 Mitochondrial affectation, DNA damage and AChE inhibition induced by Salvia officinalis essential oil on Aedes aegypti larvae. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 27 30905844
2013 AChE and RACK1 promote the anti-inflammatory properties of fluoxetine. Journal of molecular neuroscience : MN 27 24258317
2012 Cholinesterases in development: AChE as a firewall to inhibit cell proliferation and support differentiation. Chemico-biological interactions 27 23047026
2009 Typical and atypical antipsychotics alter acetylcholinesterase activity and ACHE expression in zebrafish (Danio rerio) brain. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 27 19444963
2018 Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines. Scientific reports 26 29371671
2017 Antisense miR-132 blockade via the AChE-R splice variant mitigates cortical inflammation. Scientific reports 26 28209997
2015 Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida. Bulletin of environmental contamination and toxicology 26 26293707
2009 Pro-apoptotic protein-protein interactions of the extended N-AChE terminus. Journal of neural transmission (Vienna, Austria : 1996) 26 19533292
2019 The acetylcholinesterase (AChE) inhibitor and anti-Alzheimer drug donepezil interacts with human erythrocytes. Biochimica et biophysica acta. Biomembranes 25 30904408
2020 Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602. Biomolecules 24 32414087
2022 Organophosphate insecticides disturb neuronal network development and function via non-AChE mediated mechanisms. Neurotoxicology 23 36347328
2021 TDP-43 Regulation of AChE Expression Can Mediate ALS-Like Phenotype in Zebrafish. Cells 23 33499374
2015 Acetylcholinesterase-Fc Fusion Protein (AChE-Fc): A Novel Potential Organophosphate Bioscavenger with Extended Plasma Half-Life. Bioconjugate chemistry 23 26121420
2014 Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE? Molecular neurobiology 22 25112677
2009 In contrast to anti-tumor activity, YT cell and primary NK cell cytotoxicity for Cryptococcus neoformans bypasses LFA-1. International immunology 22 19261694
1980 [Isolation and properties of DNA polymerase from extreme thermophylic bacteria Thermus aquaticus YT-1]. Biokhimiia (Moscow, Russia) 22 7378495
2022 Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer's Disease: From In Silico to In Vivo. International journal of molecular sciences 21 36361906
2019 Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men. International journal of environmental research and public health 21 30626059
2019 Prediction of AChE-ligand affinity using the umbrella sampling simulation. Journal of molecular graphics & modelling 21 31479951
2010 Altered GPI modification of insect AChE improves tolerance to organophosphate insecticides. Insect biochemistry and molecular biology 21 21112395
1998 Purification and characterisation of NADH oxidase from Thermus aquaticus YT-1 and evidence that it functions in a peroxide-reduction system. European journal of biochemistry 21 9490070
2023 Network Toxicology and Molecular Docking to Investigate the Non-AChE Mechanisms of Organophosphate-Induced Neurodevelopmental Toxicity. Toxics 20 37624215
2022 AChE as a spark in the Alzheimer's blaze - Antagonizing effect of a cyclized variant. Ageing research reviews 20 36368649
2020 Propoxur resistance associated with insensitivity of acetylcholinesterase (AChE) in the housefly, Musca domestica (Diptera: Muscidae). Scientific reports 20 32439946
2019 Clinical significance of antibodies to antigens in the ABO, MNS, P1PK, Rh, Lutheran, Kell, Lewis, Duffy, Kidd, Diego, Yt, and Xg blood group systems. Immunohematology 20 31621367
2018 Genesis of Neuroprotective Peptoid from Aβ30-34 Inhibits Aβ Aggregation and AChE Activity. ACS chemical neuroscience 20 30036464
2012 Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment. Molecular medicine reports 19 23023803
2022 Design, synthesis, and structure-activity relationship of caffeine-based triazoles as dual AChE and BACE-1 inhibitors. Drug development research 18 36161804
2022 Diterpenoids from Sigesbeckia glabrescens with anti-inflammatory and AChE inhibitory activities. Phytochemistry 18 36356673
2016 Intensified vmPFC surveillance over PTSS under perturbed microRNA-608/AChE interaction. Translational psychiatry 18 27138800
1994 The recA gene from the thermophile Thermus aquaticus YT-1: cloning, expression, and characterization. Journal of bacteriology 18 8113181
2024 PLA2G4A and ACHE modulate lipid profiles via glycerophospholipid metabolism in platinum-resistant gastric cancer. Journal of translational medicine 17 38454407
2008 Alternate AChE-R variants facilitate cellular metabolic activity and resistance to genotoxic stress through enolase and RACK1 interactions. Chemico-biological interactions 17 18572152
1989 Synergistic induction of interleukin 2 receptor (TAC) expression on YT cells by interleukin 1 or tumor necrosis factor alpha in combination with cAMP inducing agents. Cellular signalling 17 2484435
2022 Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects. Journal of biomolecular structure & dynamics 16 36325982
2012 Copy number variation in ACHE/EPHB4 (7q22) and in BCHE/MME (3q26) genes in sporadic breast cancer. Chemico-biological interactions 16 23063927
2010 Effects of IL-2 on MMP expression in freshly isolated human NK cells and the IL-2-independent NK cell line YT. Journal of immunotherapy (Hagerstown, Md. : 1997) 16 20463600
2003 High-level expression, secretion, and purification of the thermostable aqualysin I from Thermus aquaticus YT-1 in Pichia pastoris. Protein expression and purification 16 12767813
2023 Discovery of quinazolin-4(3H)-one derivatives as novel AChE inhibitors with anti-inflammatory activities. European journal of medicinal chemistry 15 37043994
2023 New Benzamides as Multi-Targeted Compounds: A Study on Synthesis, AChE and BACE1 Inhibitory Activity and Molecular Docking. International journal of molecular sciences 15 37834347
2020 shp-2 gene knockout upregulates CAR-driven cytotoxicity of YT NK cells. Vavilovskii zhurnal genetiki i selektsii 15 33659784
2019 In vitro inhibition of human red blood cell acetylcholinesterase (AChE) by temephos-oxidized products. Scientific reports 15 31611606
2018 Placental expression of AChE, α7nAChR and NF-κB in patients with preeclampsia. Ginekologia polska 15 30084476
2018 Unexpected AChE inhibitory activity of (2E)α,β-unsaturated fatty acids. Bioorganic & medicinal chemistry letters 15 30220607
2008 DNA-based typing of Kell, Kidd, MNS, Dombrock, Colton, and Yt blood group systems in the French Basques. American journal of human biology : the official journal of the Human Biology Council 14 18186512
2023 Development of Activity Rules and Chemical Fragment Design for In Silico Discovery of AChE and BACE1 Dual Inhibitors against Alzheimer's Disease. Molecules (Basel, Switzerland) 13 37110831
2019 Evaluation of the anti-conflict, reinforcing, and sedative effects of YT-III-31, a ligand functionally selective for α3 subunit-containing GABAA receptors. Journal of psychopharmacology (Oxford, England) 13 31670615
2018 In silico identification of AChE and PARP-1 dual-targeted inhibitors of Alzheimer's disease. Journal of molecular modeling 13 29869722
2005 Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion. Chemico-biological interactions 13 16289062
2000 The cAMP-dependent protein kinase mediates the expression of AChE in chick myotubes. Neuroreport 13 10757523
1992 Induction and function of Fc epsilon RII on YT cells; possible role of ADF/thioredoxin in Fc epsilon RII expression. Immunobiology 13 1452201
2023 Antibacterial and antibiofilm potential of Lacticaseibacillus rhamnosus YT and its cell-surface extract. BMC microbiology 12 36635630
2022 In silico analyses of acetylcholinesterase (AChE) and its genetic variants in interaction with the anti-Alzheimer drug Rivastigmine. Journal of cellular biochemistry 12 35644025
2019 Target-site mutations (AChE-G119S and kdr) in Guangxi Anopheles sinensis populations along the China-Vietnam border. Parasites & vectors 12 30732643
1999 Identification, cloning and expression of p25, an AT-rich DNA-binding protein from the extreme thermophile, Thermus aquaticus YT-1. Nucleic acids research 12 10076001
2023 Identification of New N-methyl-piperazine Chalcones as Dual MAO-B/AChE Inhibitors. Pharmaceuticals (Basel, Switzerland) 11 36678580
2021 Acetylcholinesterase (AChE) Activity in Embryos of Zebrafish. Methods in molecular biology (Clifton, N.J.) 11 33423231
2020 Acetylcholinesterase (AChE) monoclonal antibody generation and validation for use as a biomarker of glyphosate-based herbicide exposure in commercial freshwater fish. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 11 33346154
2007 Inhibition of AChE by single and simultaneous exposure to malathion and its degradation products. General physiology and biophysics 11 18281741
2006 Differential effects of proteasome inhibitors on cell cycle and apoptotic pathways in human YT and Jurkat cells. Journal of cellular biochemistry 11 16173095
2005 Expression of acetylcholinesterase (AChE) and aryl acylamidase (AAA) during early zebrafish embryogenesis. Chemico-biological interactions 11 16425445
2019 Repeated bifenthrin exposure alters hippocampal Nurr-1/AChE and induces depression-like behavior in adult rats. Behavioural brain research 10 30978409
2008 Transcriptional control of different subunits of AChE in muscles: signals triggered by the motor nerve-derived factors. Chemico-biological interactions 10 18514177
1987 The Yt blood group system (ISBT No. 011). Genetic studies. Vox sanguinis 10 3477904
2023 Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility. PloS one 9 37027384
2022 Design, synthesis and biological evaluation of light-driven on-off multitarget AChE and MAO-B inhibitors. RSC medicinal chemistry 9 35923722

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