Affinage

APLP1

Amyloid beta precursor like protein 1 · UniProt P51693

Length
650 aa
Mass
72.2 kDa
Annotated
2026-04-28
45 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

APLP1 is a type I transmembrane glycoprotein of the amyloid precursor protein family that functions primarily as a synaptic cell adhesion molecule and modulator of neuronal signaling. APLP1 localizes predominantly to the cell surface, where zinc-dependent oligomerization through its E2 domain drives trans-cellular dimerization, induces presynaptic differentiation, and maintains excitatory synapse density and spine number in vivo (PMID:28450540, PMID:24855651, PMID:19126676). It undergoes α-, β-, γ-, and ε-secretase processing—uniquely including direct γ-secretase cleavage of the full-length protein without prior ectodomain shedding, determined by its transmembrane sequence—generating an intracellular domain that forms transcriptionally active complexes with Mint3/Taz(Yap) and transactivates the neprilysin promoter (PMID:29382944, PMID:15944124, PMID:21178287). Beyond canonical secretase biology, APLP1 interacts with LAG3 to mediate pathological α-synuclein fibril internalization and neurotoxicity, binds the SARM1 auto-inhibitory domain to maintain axonal NAD⁺ levels and prevent axon degeneration, promotes NMDA receptor surface expression via GluN1 binding, regulates Cav2.3 internalization, and is a p53 transcriptional target that augments neural cell apoptosis (PMID:38821932, PMID:41324805, PMID:25683482, PMID:22178872, PMID:17533371).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2004 High

    Establishing that APLP1, like APP, is a sequential secretase substrate resolved whether non-amyloidogenic APP family members undergo the same regulated intramembrane proteolysis cascade, and revealed that N-glycosylation uniquely modulates APLP1 processing.

    Evidence Pharmacological dissection with α- and γ-secretase inhibitors in stably transfected SH-SY5Y cells with fragment detection by immunoblot

    PMID:14970212

    Open questions at the time
    • Identity and aggregation potential of APLP1-derived peptides not yet determined
    • In vivo secretase processing rates not measured
  2. 2005 High

    Demonstrating that the APLP1 intracellular domain transactivates the neprilysin promoter in a presenilin-dependent manner established a functional output of γ-secretase cleavage and linked APP family processing to Aβ-degrading enzyme regulation.

    Evidence Neprilysin promoter-reporter assays, γ-secretase inhibitor treatment, and PS1/PS2 knockout cells

    PMID:15944124

    Open questions at the time
    • Endogenous neprilysin regulation by APLP1-AICD not confirmed in vivo
    • Relative contribution of APLP1 versus APP AICD to neprilysin expression unclear
  3. 2006 High

    Identification of PAT1a as a direct binding partner of the APLP1 basolateral sorting signal, modulating its surface levels and trafficking through TGN/endosomal compartments, revealed a mechanism controlling APLP1 polarized delivery in neurons.

    Evidence Co-IP, co-localization in primary neurons, RNAi knockdown, and cell-surface biotinylation

    PMID:17050537

    Open questions at the time
    • In vivo consequences of PAT1a loss on APLP1-dependent synaptic functions not tested
    • Structural basis of PAT1a–APLP1 interaction unknown
  4. 2007 High

    Identifying APLP1 as a direct p53 transcriptional target that promotes neural cell apoptosis placed APLP1 within stress-response and senescence pathways beyond its adhesion and processing biology.

    Evidence p53-responsive element validation by EMSA and reporter assay, siRNA knockdown, and overexpression apoptosis assays in neuroblastoma cells

    PMID:17533371

    Open questions at the time
    • Downstream apoptotic mechanism triggered by APLP1 not defined
    • Relevance to neurodegeneration in vivo not assessed
  5. 2009 High

    Three concurrent studies established that APLP1 uniquely among APP family members localizes predominantly to the cell surface and forms robust trans-cellular interactions, that β- and γ-secretase generate APLP1-derived Aβ-like peptides (APL1β) detectable in human CSF whose spectrum parallels Aβ42 shifts caused by presenilin mutations, and that the α/γ-derived p3-like peptide is non-toxic and non-aggregating.

    Evidence Live-cell FRET and co-IP for surface/trans interactions; mass spectrometry of CSF peptides with γ-secretase modulator and PS1 mutant studies; aggregation and neurotoxicity assays for the p3-like peptide

    PMID:19126676 PMID:19401174 PMID:20049724

    Open questions at the time
    • Physiological function of APL1β peptides unknown
    • Whether CSF APL1β serves as a biomarker requires clinical validation
  6. 2011 High

    Structural, biophysical, and cell-biological advances revealed the conserved antiparallel E2-domain dimer interface with heparin-binding residues, showed APLP1/APLP2 form Mint3/Taz(Yap) nuclear transactivation complexes after γ-secretase cleavage, identified APLP1 as a binding partner and internalization driver of Cav2.3, and demonstrated autophagy-lysosome-mediated APLP1 degradation under ER stress.

    Evidence X-ray crystallography at 2.1 Å with mutagenesis and AUC; co-IP and transcriptional reporter assays with Mint3/Taz/Yap; yeast two-hybrid plus co-IP and endocytosis assays for Cav2.3; pharmacological and genetic autophagy modulation in neuronal cells

    PMID:21178287 PMID:21574595 PMID:21626267 PMID:22178872

    Open questions at the time
    • Transcriptional targets of APLP1-Mint3-Taz/Yap complexes beyond neprilysin not identified
    • Physiological relevance of Cav2.3 regulation by APLP1 in neurons not confirmed in vivo
    • Autophagy-dependent APLP1 degradation not demonstrated in vivo
  7. 2014 High

    Zinc was identified as a specific inducer of APLP1 E2-domain oligomerization and plasma membrane clustering, distinguishing APLP1 from APLP2 in metal-ion-regulated adhesion and explaining how synaptic zinc could locally control APLP1 function.

    Evidence Live-cell FRET, deletion mutant analysis, and biochemical zinc/copper binding assays

    PMID:24855651

    Open questions at the time
    • Whether endogenous synaptic zinc concentrations are sufficient to drive APLP1 clustering in vivo not established
    • Downstream signaling consequences of zinc-induced APLP1 clusters unknown
  8. 2015 High

    Multiple studies demonstrated that APLP1 promotes NMDA receptor surface expression via GluN1 interaction, that its E2 domain recognizes heparanase-processed heparin termini in a structurally defined manner, and that APLP1-KO mice exhibit increased excitatory transmission with reduced network inhibition in dentate gyrus.

    Evidence Co-IP from brain and HEK cells with surface biotinylation; crystal structures of APLP1 E2-heparin complexes at 2.5 Å; in vivo field recordings in APLP1-KO mice

    PMID:25683482 PMID:25728909 PMID:25760599

    Open questions at the time
    • Whether NMDA receptor surface modulation underlies the KO electrophysiological phenotype not tested directly
    • Behavioral consequences of altered E/I balance in APLP1-KO not characterized at this time point
  9. 2016 Medium

    Zinc-dependent multimerization was shown to protect APLP1 from secretase cleavage and enrich it at cellular adhesion sites, establishing a feedback mechanism where metal ions stabilize APLP1 adhesion complexes by simultaneously promoting oligomerization and blocking ectodomain shedding.

    Evidence Live-cell microscopy, microcontact printing adhesion assay, and ELISA for secreted ectodomains in cell culture and rat neurons

    PMID:26801522

    Open questions at the time
    • In vivo relevance at synaptic zinc concentrations not confirmed
    • Whether zinc protection from cleavage applies to β-secretase processing not addressed
  10. 2017 High

    APLP1 was definitively established as a synaptogenic cell adhesion molecule: it induces presynaptic differentiation in a heterologous assay, trans-dimerizes more robustly than APP due to low endocytosis, and its loss in aged mice reduces excitatory synapse number (mEPSC frequency, spine density).

    Evidence Heterologous synaptogenesis coculture assay, live-cell imaging, mEPSC recordings, and spine density analysis in KO mice

    PMID:28450540

    Open questions at the time
    • Postsynaptic signaling cascade downstream of APLP1 trans-dimerization not defined
    • Whether APLP1 synaptogenic activity requires its intracellular domain or secretase cleavage not tested
  11. 2018 High

    Discovery that γ-secretase directly cleaves full-length APLP1 without prior ectodomain shedding—a unique property determined by its transmembrane sequence—revealed a non-canonical γ-secretase substrate recognition mechanism and generated a novel secreted fragment (sAPLP1γ).

    Evidence Mass spectrometry identification of cleavage products, γ-secretase inhibitor treatment, and transmembrane domain swap experiments in HEK cells

    PMID:29382944

    Open questions at the time
    • Function of sAPLP1γ fragment unknown
    • Structural basis for how APLP1 TMD allows direct γ-secretase access not resolved
  12. 2020 High

    Identification of matriptase as a novel sheddase that cleaves APLP1 at Arg124 in the E1 domain and reduces homodimerization revealed a new layer of APLP1 ectodomain regulation independent of canonical secretases.

    Evidence Co-IP, in cellulo cleavage assay, Arg124Ala mutagenesis abolishing cleavage, and BRET homodimerization assay

    PMID:32572095

    Open questions at the time
    • Physiological context where matriptase cleaves APLP1 in the brain not defined
    • Impact on synaptic adhesion function not assessed
  13. 2024 High

    APLP1 was identified as a co-receptor with LAG3 for pathological α-synuclein fibrils, with double knockout eliminating dopaminergic neuron loss, thereby positioning APLP1 as a central mediator of α-synuclein cell-to-cell transmission and Parkinson's-relevant neurodegeneration.

    Evidence Co-IP for APLP1-LAG3 interaction, α-syn PFF internalization assays, single and double KO mouse models with behavioral and histological endpoints, anti-LAG3 antibody blocking

    PMID:38821932

    Open questions at the time
    • Whether APLP1 directly binds α-synuclein fibrils or acts solely through LAG3 not resolved
    • Relevance to endogenous α-synuclein spreading in human PD brain not established
  14. 2025 Medium

    APLP1 was found to bind the SARM1 auto-inhibitory domain and maintain axonal NAD⁺ levels; its loss triggers SARM1-dependent axon degeneration, establishing APLP1 as a cell-intrinsic axon maintenance factor beyond its adhesion role.

    Evidence Yeast two-hybrid screen, co-IP confirmation, siRNA knockdown with NAD⁺ quantification, and axon degeneration rescue in SARM1 KO background

    PMID:41324805

    Open questions at the time
    • Mechanism by which APLP1 keeps SARM1 auto-inhibited (direct allosteric versus indirect) not defined
    • Not independently replicated
    • In vivo validation in APLP1-KO mice for axon degeneration phenotype not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the physiological functions of APLP1-derived secreted peptides (APL1β, sAPLP1γ), the postsynaptic signaling cascade downstream of APLP1 trans-synaptic adhesion, and whether APLP1's roles in α-synuclein transmission and SARM1-dependent axon maintenance converge in neurodegenerative disease.
  • No substrate or signaling pathway downstream of APLP1 adhesion identified
  • Structural basis of APLP1-LAG3-α-synuclein ternary complex unknown
  • Relative in vivo contributions of APLP1 adhesion versus intracellular signaling to synapse maintenance not dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 2 GO:0140110 transcription regulator activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 1 GO:0005764 lysosome 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-5357801 Programmed Cell Death 1
Partners
APBA3CACNA1EGRIN1LAG3PAT1SARM1ST14

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The intracellular domain (AICD) of APLP1, generated by presenilin-dependent γ-secretase cleavage, transactivates the neprilysin gene promoter, thereby regulating neprilysin transcription and activity in a presenilin-dependent manner. Transient expression of AICD constructs, neprilysin promoter-reporter transactivation assays, γ-secretase inhibitor pharmacology, PS1/PS2 knockout cells Neuron High 15944124
2004 APLP1 undergoes α-, γ-, and ε-like secretase cleavages analogous to APP, producing intracellular domain fragments and p3-like peptides; uniquely among APP family members, APLP1 processing is modulated by N-glycosylation. C-terminally tagged constructs in stably transfected SH-SY5Y cells, specific protease inhibitors (α- and γ-secretase), detection of C-terminal fragments and secreted peptides by immunoblot and ELISA The Journal of biological chemistry High 14970212
2009 APLP1 localizes predominantly to the cell surface (unlike APP and APLP2 which are mostly intracellular), forms trans-cellular interactions (not observed for APP or APLP2), and engages in homo- and heterotypic cis interactions with APP family members; coexpression with APP or APLP2 reduces Aβ42 generation, attributed to heteromeric complex formation. Live-cell imaging, FRET, co-immunoprecipitation, deletion mutant analysis in transfected cells Journal of cell science High 19126676
2006 PAT1a binds directly to the basolateral sorting signal of APLP1 (and APP/APLP2), co-localizes with APLP1 in trans-Golgi network vesicles/endosomes in primary neurons, and modulates APLP1 levels at the cell surface; PAT1a overexpression or knockdown alters APP/APLP processing and Aβ secretion. Co-immunoprecipitation in vivo, co-localization in primary neurons, RNAi knockdown and overexpression, cell-surface biotinylation assay The Journal of biological chemistry High 17050537
2009 γ-Secretase processing of APLP1 generates an ~3.5 kDa p3-like peptide (ALP-1) that does not aggregate and is not toxic to neurons; β-secretase inhibition does not abolish its production, confirming it arises from the α/γ pathway. Stable transfection in CHO cells, γ- and β-secretase-specific inhibitors, novel anti-APLP1 antibody detection, neuronal toxicity and aggregation assays Brain research Medium 19401174
2009 APLP1-derived Aβ-like peptides (APL1β25, APL1β27, APL1β28) are generated by β- and γ-secretase cleavages in the CNS; γ-secretase modulators and familial AD presenilin1 mutations that increase Aβ42 production cause a parallel increase in APL1β28, indicating shared γ-secretase cleavage site selectivity. Mass spectrometry identification of CSF peptides, cell-based γ-secretase modulator and presenilin mutant studies, CSF analysis from presenilin1 mutation carriers and sporadic AD patients EMBO molecular medicine High 20049724
2011 APLP1 is degraded through the autophagy-lysosome pathway in neuronal cells in response to proteasome inhibition; ER stress induced by proteasome inhibitors activates autophagy, causing reduction of mature APLP1; blocking autophagy or JNK rescues APLP1 expression. Proteasome inhibitor treatment, autophagy inhibition (pharmacological and genetic), JNK inhibition, immunoblot quantification in neuronal cells Protein & cell Medium 21626267
2011 APLP1 E2 domain forms an antiparallel dimer, and heparin binding induces E2 dimerization; the same conserved dimerization mode is shared between APP and APLP1 E2 domains; residues Arg-369 and His-433 at the dimeric interface mediate heparin binding. X-ray crystallography (2.1 Å resolution crystal structures of APP and APLP1 E2 domains), analytical ultracentrifugation, heparin-binding assays, site-directed mutagenesis Biochemistry High 21574595
2011 APLP1 and APLP2 form transcriptionally active triple protein complexes with adaptor protein Mint3 and transcriptional co-activators Taz or Yap following γ-secretase cleavage; Mint1 (in place of Mint3) prevents nuclear translocation of the complex; APLP1 shows lower transactivation levels than APP and APLP2. Co-immunoprecipitation, nuclear fractionation, transcriptional reporter assays, γ-secretase inhibitor treatment Journal of Alzheimer's disease : JAD Medium 21178287
2014 Zinc ions bind to a novel site in the APLP1 E2 domain and specifically induce APLP1 oligomerization and clustering at the plasma membrane; the APLP2 E2 domain binds zinc more weakly and remains monomeric; copper ions bind all three family members' E2 domains. FRET analyses in live cells, deletion mutant analysis, biochemical zinc/copper binding assays, fluorescence microscopy The Journal of biological chemistry High 24855651
2015 APLP1 co-immunoprecipitates with GluN1/GluN2A and GluN1/GluN2B NMDA receptor subtypes via interaction with the obligatory GluN1 subunit in mammalian cells and adult brain; APLP1 overexpression enhances GluN1/GluN2A and GluN1/GluN2B cell surface expression. Co-immunoprecipitation from transfected HEK cells and detergent extracts of adult brain; cell-surface biotinylation assay Journal of neurochemistry Medium 25683482
2015 Crystal structures of APLP1 E2 domain reveal two distinct heparin-binding modes: specific recognition of heparanase-processed heparin termini involving the nonreducing end, and continuous chain binding via a positively charged surface patch; the apo structure shows a flexible N-terminal helix αA. X-ray crystallography at 2.5 Å (apo and APLP1 E2-heparin dodecasaccharide complex structures) Acta crystallographica. Section D, Biological crystallography High 25760599
2015 APLP1 deletion in mice leads to increased excitatory synaptic transmission and decreased paired-pulse inhibition (reduced network inhibition) in dentate gyrus without impairing short-term or long-term synaptic plasticity. In vivo field excitatory postsynaptic potential recordings, paired-pulse inhibition analysis, LTP and STP measurements in APLP1-KO mice The Journal of comparative neurology Medium 25728909
2016 Zinc induces multimerization of APLP1 and APP and enriches them at cellular adhesion sites, forming de novo APLP1-containing adhesion complexes; zinc-binding also prevents cleavage of APLP1 by extracellular secretases; APLP1 shows stronger zinc-dependent adhesion than APP or APLP2. Live-cell microscopy, microcontact printing adhesion assay, ELISA for secreted ectodomains, zinc treatment in cell culture and rat neurons Journal of neurochemistry Medium 26801522
2017 APLP1 functions as a synaptic cell adhesion molecule: it localizes pre- and post-synaptically, induces presynaptic differentiation in contacting axons when expressed in non-neuronal cells, forms trans-cellular dimers more robustly than APP (due to reduced endocytosis and elevated surface levels), and its loss in aged mice causes reduced mEPSC frequency and reduced spine density. Heterologous synaptogenesis assay (non-neuronal cell/neuron coculture), live-cell imaging, electrophysiology (mEPSC recording), spine density analysis in KO mice, endocytosis assays, Co-IP for Mint/X11 interaction The Journal of neuroscience High 28450540
2018 Full-length APLP1 (but not APP or APLP2) is uniquely cleaved by γ-secretase without prior ectodomain shedding, generating a novel fragment termed sAPLP1γ; the APLP1 transmembrane sequence is the critical determinant for this direct γ-secretase cleavage and is sufficient to convert larger type-I proteins like APP into direct γ-secretase substrates. Stable transfection in HEK cells, γ-secretase inhibitor treatment, mass spectrometry, transmembrane sequence swap experiments, immunoblot analysis Scientific reports High 29382944
2020 Matriptase directly interacts with APLP1 and cleaves it in its E1 ectodomain at Arg124; this cleavage reduces APLP1 homodimerization as measured by BRET; Arg124Ala mutation abolishes matriptase processing of APLP1. Co-immunoprecipitation, in cellulo cleavage assay with matriptase, site-directed mutagenesis (Arg124Ala), BRET homodimerization assay Scientific reports High 32572095
2024 APLP1 interacts with LAG3 to facilitate binding, internalization, transmission, and toxicity of pathologic α-synuclein preformed fibrils (PFFs); deletion of both Aplp1 and Lag3 eliminates dopaminergic neuron loss and behavioral deficits induced by α-syn PFF; anti-LAG3 blocks α-syn PFF internalization by disrupting the Aplp1-Lag3 interaction. Co-immunoprecipitation (Aplp1-Lag3 interaction), α-syn PFF internalization assays, Aplp1/Lag3 single and double knockout mouse models, behavioral testing, dopaminergic neuron counting, anti-LAG3 antibody blocking experiments Nature communications High 38821932
2025 APLP1 binds to the auto-inhibitory domain of SARM1 (identified by yeast two-hybrid screen, confirmed by co-immunoprecipitation); APLP1 levels increase in proximal axon segments after injury; Aplp1 knockdown reduces neuronal NAD+ levels and causes spontaneous SARM1-dependent axon degeneration, and accelerates injury-induced axonal degeneration. Yeast two-hybrid screen, co-immunoprecipitation, Aplp1 siRNA knockdown in sensory neurons, NAD+ quantification, in vitro axon degeneration assay in SARM1 KO background Molecular neurobiology Medium 41324805
2011 APLP1 binds to the II-III loop of the voltage-gated calcium channel Cav2.3 (identified by yeast two-hybrid, confirmed by co-immunoprecipitation) and promotes internalization of Cav2.3; Rab5A also binds the same loop and inhibits APLP1-mediated channel internalization. Yeast two-hybrid screen, co-immunoprecipitation, surface biotin endocytosis assay, patch-clamp recordings in HEK-293 cells stably expressing Cav2.3 Cellular physiology and biochemistry Medium 22178872
2007 APLP1 is a direct transcriptional target of p53, with a functional p53 responsive element in the first intron of the APLP1 gene; APLP1 is induced in a p53-dependent manner during senescence; APLP1 knockdown reduces stress-induced apoptosis of neural cells, while ectopic APLP1 expression augments it. DNA microarray, in vivo and in vitro characterization of p53 responsive element (EMSA, reporter assay), siRNA knockdown, ectopic overexpression in neuroblastoma cells with apoptosis readout Oncogene High 17533371

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron 289 15944124
2004 The proteolytic processing of the amyloid precursor protein gene family members APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages: modulation of APLP-1 processing by n-glycosylation. The Journal of biological chemistry 181 14970212
2008 Increased APLP1 expression and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. Journal of neurochemistry 95 18284614
2009 Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2. Journal of cell science 79 19126676
2014 Comparative analysis of single and combined APP/APLP knockouts reveals reduced spine density in APP-KO mice that is prevented by APPsα expression. Acta neuropathologica communications 76 24684730
2009 The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42 production in the central nervous system. EMBO molecular medicine 74 20049724
2010 APLP1, Alzheimer's-like pathology and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. Neurotoxicology 61 20188756
2017 APLP1 Is a Synaptic Cell Adhesion Molecule, Supporting Maintenance of Dendritic Spines and Basal Synaptic Transmission. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 28450540
2011 APP and APLP1 are degraded through autophagy in response to proteasome inhibition in neuronal cells. Protein & cell 59 21626267
2011 The role of APP and APLP for synaptic transmission, plasticity, and network function: lessons from genetic mouse models. Experimental brain research 45 22006270
2004 Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 15208260
2011 Structural aspects and physiological consequences of APP/APLP trans-dimerization. Experimental brain research 37 21952790
2010 Neurons generated from APP/APLP1/APLP2 triple knockout embryonic stem cells behave normally in vitro and in vivo: lack of evidence for a cell autonomous role of the amyloid precursor protein in neuronal differentiation. Stem cells (Dayton, Ohio) 33 20049903
2006 PAT1a modulates intracellular transport and processing of amyloid precursor protein (APP), APLP1, and APLP2. The Journal of biological chemistry 33 17050537
2024 Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein. Nature communications 32 38821932
2011 The E2 domains of APP and APLP1 share a conserved mode of dimerization. Biochemistry 31 21574595
2007 Amyloid-beta precursor-like protein APLP1 is a novel p53 transcriptional target gene that augments neuroblastoma cell death upon genotoxic stress. Oncogene 31 17533371
2018 APLP1 is endoproteolytically cleaved by γ-secretase without previous ectodomain shedding. Scientific reports 27 29382944
2015 APLP1 and APLP2, members of the APP family of proteins, behave similarly to APP in that they associate with NMDA receptors and enhance NMDA receptor surface expression. Journal of neurochemistry 27 25683482
2011 Signaling via amyloid precursor-like proteins APLP1 and APLP2. Journal of Alzheimer's disease : JAD 25 21178287
2003 Accumulation of the amyloid precursor-like protein APLP2 and reduction of APLP1 in retinoic acid-differentiated human neuroblastoma cells upon curcumin-induced neurite retraction. Brain research. Molecular brain research 25 14597230
1998 Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1. Human genetics 21 9521588
2016 Amyloid precursor-like protein 1 (APLP1) exhibits stronger zinc-dependent neuronal adhesion than amyloid precursor protein and APLP2. Journal of neurochemistry 20 26801522
2014 Novel zinc-binding site in the E2 domain regulates amyloid precursor-like protein 1 (APLP1) oligomerization. The Journal of biological chemistry 20 24855651
2009 gamma-secretase processing of APLP1 leads to the production of a p3-like peptide that does not aggregate and is not toxic to neurons. Brain research 17 19401174
2015 Deletion of the amyloid precursor-like protein 1 (APLP1) enhances excitatory synaptic transmission, reduces network inhibition but does not impair synaptic plasticity in the mouse dentate gyrus. The Journal of comparative neurology 15 25728909
2015 Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes. Acta crystallographica. Section D, Biological crystallography 12 25760599
1996 Characterization of the genomic structure of the mouse APLP1 gene. Genomics 12 8786110
2015 APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment. Alzheimer's research & therapy 9 26689589
2023 Comparative binding analysis of WGX50 and Alpha-M with APP family proteins APLP1 and APLP2 using structural-dynamics and free energy calculation approaches. Physical chemistry chemical physics : PCCP 8 37199163
2021 Rapid evolution of mammalian APLP1 as a synaptic adhesion molecule. Scientific reports 8 34050225
2015 APLP1 promotes dFoxO-dependent cell death in Drosophila. Apoptosis : an international journal on programmed cell death 8 25740230
2017 Amyloid-precursor Like Proteins APLP1 and APLP2 Are Dispensable for Normal Development of the Neonatal Respiratory Network. Frontiers in molecular neuroscience 6 28690498
2025 Blood-derived APLP1+ extracellular vesicles are potential biomarkers for the early diagnosis of brain diseases. Science advances 5 39742488
2011 APLP1 and Rab5A interact with the II-III loop of the voltage-gated Ca-channel Ca(v)2.3 and modulate its internalization differently. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 5 22178872
2022 Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory. Frontiers in molecular neuroscience 3 36385765
2016 Multiplex APLP System for High-Resolution Haplogrouping of Extremely Degraded East-Asian Mitochondrial DNAs. PloS one 3 27355212
2012 [Species identification of animal hair present as a contaminant in food by PCR-APLP method]. Shokuhin eiseigaku zasshi. Journal of the Food Hygienic Society of Japan 3 23132356
2016 Genotyping of the c.1423C>T (p.P475S) polymorphism in the ADAMTS13 gene by APLP and HRM assays: Northeastern Asian origin of the mutant. Legal medicine (Tokyo, Japan) 2 27497325
2015 The art of traditional native PAGE: The APLP 48-ID assay for human identification. Legal medicine (Tokyo, Japan) 2 26980250
2009 Down-regulation of APLP1 mRNA expression in hippocampus of pilocarpine-induced epileptic rats. Neuroscience bulletin 2 19448684
2020 Matriptase processing of APLP1 ectodomain alters its homodimerization. Scientific reports 1 32572095
2000 [Application of the PCR-APLP method to determine ABO genotypes in forensic samples]. Nihon hoigaku zasshi = The Japanese journal of legal medicine 1 11060991
2025 Assessing Plasma APLP1 for the Progression of Parkinson's Disease: Insights from HSPD and PPMI Cohorts. Movement disorders : official journal of the Movement Disorder Society 0 39968922
2025 APLP1 Interacts with SARM1 and Regulates Axonal Maintenance and Post-Injury Degeneration. Molecular neurobiology 0 41324805