Affinage

TRPM2

Transient receptor potential cation channel subfamily M member 2 · UniProt O94759

Round 2 corrected
Length
1503 aa
Mass
171.2 kDa
Annotated
2026-04-28
130 papers in source corpus 30 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRPM2 is a Ca2+-permeable, non-selective cation channel that couples intracellular ADP-ribose (ADPR) sensing to Ca2+ (and Zn2+) entry, thereby transducing oxidative stress, metabolic, and inflammatory signals into diverse cellular outcomes including cell death, autophagy inhibition, inflammasome activation, and endothelial barrier regulation. The channel is gated by ADPR binding to the MHR1/2 cleft and by Ca2+ binding to transmembrane sites; cryo-EM structures show that ADPR rotates MHR1/2 and disrupts intersubunit NUDT9-H contacts while Ca2+ opens the lower gate, and additional agonists including 2′-deoxy-ADPR (a superagonist), cADPR, and bilirubin (an extracellular agonist acting independently of ADPR) expand the activation repertoire (PMID:30250252, PMID:30467180, PMID:28671679, PMID:36921602). TRPM2-mediated Ca2+ influx drives downstream signaling through CAMK2-dependent BECN1 phosphorylation to inhibit autophagy, calcineurin-dependent GSK-3β dephosphorylation relevant to bipolar disorder-like phenotypes, caspase/PARP-mediated apoptosis, NLRP3 inflammasome priming, and MCU/ALOX12-dependent ferroptosis (PMID:27245989, PMID:26311765, PMID:16306129, PMID:37275121). Beyond plasma-membrane Ca2+ entry, TRPM2 functions as a lysosomal Ca2+/Zn2+ release channel—lysosomal Zn2+ mobilization drives mitochondrial fission and β-cell death, while lysosomal TRPM2 supports dendritic cell chemotaxis—and physically associates with extrasynaptic NMDARs to promote their surface expression and excitotoxicity, and with CD36 to amplify oxLDL uptake and atherogenesis (PMID:25562606, PMID:28753206, PMID:21753080, PMID:35421327).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    The foundational question of TRPM2's ligand identity and ion selectivity was answered: ADPR directly gates TRPM2 as a Ca2+-permeable nonselective cation channel via a C-terminal NUDT9 homology domain, establishing ADPR as a novel intracellular second messenger for Ca2+ entry.

    Evidence Whole-cell and single-channel patch-clamp in HEK-293 cells and native U937 monocytes/immunocytes, biochemical identification of NUDT9-H domain

    PMID:11385575 PMID:11509734

    Open questions at the time
    • Whether NUDT9-H retains enzymatic ADPRase activity in vertebrate TRPM2 was unknown
    • Structural basis of ADPR recognition unresolved
    • Physiological source of ADPR in vivo not established
  2. 2002 High

    TRPM2 was shown to be a sensor of oxidative stress: H2O2 and ROS activate the channel through a mechanism partially independent of the ADPR-binding Nudix domain, as demonstrated by a splice variant lacking this region, linking TRPM2 to redox-sensitive cell death.

    Evidence Patch-clamp and Ca2+ imaging with H2O2/TNFα stimulation; antisense knockdown; functional characterization of NUDT9-H-deleted splice variant in HEK-293 cells

    PMID:11804595 PMID:11960981

    Open questions at the time
    • Exact ROS-sensing mechanism (direct oxidation vs. intermediate metabolite generation) unresolved
    • Whether PARP-dependent ADPR generation is required for all ROS-mediated activation unclear
  3. 2003 High

    Discovery of the dominant-negative splice isoform TRPM2-S demonstrated that channel oligomerization is functionally regulatable: TRPM2-S directly interacts with full-length TRPM2-L and suppresses H2O2-induced Ca2+ influx and cell death.

    Evidence Co-immunoprecipitation, confocal localization, Ca2+ influx and cell death assays in HEK-293T cells

    PMID:12594222

    Open questions at the time
    • Stoichiometry of TRPM2-S/L heteromers unknown
    • Physiological regulation of TRPM2-S expression not defined
  4. 2005 High

    The downstream cell-death mechanism was mapped: TRPM2-dependent Ca2+ entry activates caspases-8, -9, -3, -7 and PARP cleavage, and intracellular Ca2+ chelation fully blocks this cascade, establishing Ca2+ as the critical intermediary between channel opening and apoptosis.

    Evidence Retroviral overexpression/knockdown of TRPM2 isoforms in U937 cells; BAPTA-AM chelation; caspase/PARP western blot

    PMID:16306129

    Open questions at the time
    • Whether Zn2+ contributes alongside Ca2+ was not yet explored
    • Cell-type specificity of the apoptotic pathway not addressed
  5. 2007 High

    TRPM2 was placed in endothelial barrier function: H2O2-stimulated ADPR formation opens TRPM2 in endothelial cells, causing Ca2+ entry and increased permeability; siRNA or dominant-negative TRPM2-S suppresses this response.

    Evidence Patch-clamp, fura-2 imaging, transendothelial electrical resistance in primary endothelial cells with siRNA and dominant-negative approaches

    PMID:18048770

    Open questions at the time
    • Downstream targets linking TRPM2 Ca2+ to junctional disassembly (e.g., VE-cadherin phosphorylation) not yet identified
  6. 2009 High

    An ADPR-independent gating mechanism was uncovered: intracellular Ca2+ alone activates TRPM2 via an N-terminal calmodulin-binding domain, explaining how ADPR-insensitive splice variants retain channel function and establishing Ca2+ as both a co-agonist and a standalone gating signal.

    Evidence Patch-clamp with ADPR-binding-site mutations; CaM-binding domain identification; intact cell activation assays

    PMID:19372375

    Open questions at the time
    • CaM-TRPM2 interface not structurally resolved
    • Relative contribution of CaM-dependent vs. transmembrane Ca2+-binding-site gating unknown
  7. 2011 High

    TRPM2 was shown to function as an intracellular (endolysosomal) Ca2+ release channel in dendritic cells, expanding its role beyond plasma membrane Ca2+ entry and linking it to immune cell chemotaxis and maturation.

    Evidence TRPM2-KO mice and siRNA knockdown; endolysosomal confocal localization; Ca2+ signaling and in vitro/in vivo chemotaxis assays in DCs

    PMID:21753080

    Open questions at the time
    • How TRPM2 is targeted to lysosomes vs. plasma membrane not defined
    • Whether lysosomal TRPM2 gating uses the same ADPR/Ca2+ mechanism unclear
  8. 2015 High

    Three key downstream signaling axes were mapped: (1) lysosomal Zn2+ release (not Ca2+ alone) mediates β-cell apoptosis; (2) Ca2+-dependent calcineurin activation dephosphorylates GSK-3β (relevant to bipolar disorder); (3) TRPM2-mediated Ca2+ maintains cardiac mitochondrial function during ischemia-reperfusion, as confirmed by loss-of-function mutant rescue in KO cardiomyocytes.

    Evidence TRPM2-KO mice, Zn2+ chelation/imaging in islets, calcineurin inhibitor experiments plus D543E mutant analysis, and adenoviral rescue with E960D/P1018L mutants in KO hearts

    PMID:25562606 PMID:25576627 PMID:26311765

    Open questions at the time
    • Mechanism of TRPM2-dependent lysosomal Zn2+ permeation not structurally resolved
    • Whether GSK-3β regulation is cell-type-specific beyond neurons unclear
    • Identity of cardiac TRPM2 agonist in ischemia-reperfusion not determined
  9. 2016 High

    TRPM2 was positioned as an autophagy regulator: TRPM2-mediated Ca2+ activates CAMK2, which phosphorylates BECN1 at Ser295 to disrupt BECN1-PIK3C3 association and promote BECN1-BCL2 binding, thereby inhibiting autophagy induction during oxidative stress.

    Evidence TRPM2 KO/inhibition; CAMK2 phosphorylation assays; BECN1 Co-IP with PIK3C3/BCL2; S295 mutagenesis; autophagy flux assays; acetaminophen liver injury model

    PMID:27245989

    Open questions at the time
    • Whether autophagy inhibition is a general consequence of TRPM2 activation across tissues not tested
    • CAMK2 isoform specificity not established
  10. 2017 High

    Multiple advances refined TRPM2 pharmacology, structure-activity relationships, and tissue-specific signaling: 2′-deoxy-ADPR was identified as an endogenous superagonist; Arg1433/Tyr1349 in NUDT9-H were identified as critical ADPR-binding residues; lysosomal Zn2+ was linked to palmitate-induced mitochondrial fission via Drp-1; neutrophil ROS-TRPM2-VE-cadherin phosphorylation was established as the mechanism for endothelial barrier opening and transendothelial migration; and a PKC/NOX/PARP-1→TRPM2→PYK2/MEK/ERK positive feedback loop was mapped in microglia.

    Evidence Electrophysiology with synthetic ADPR analogues; mass spectrometry for endogenous 2′-deoxy-ADPR; conditional EC-TRPM2-KO mice with VE-cadherin phosphorylation assays; TRPM2-KO microglia with pharmacological inhibitor panels; Zn2+/Ca2+ imaging with Drp-1 recruitment in human islets

    PMID:28322340 PMID:28515263 PMID:28671679 PMID:28753206 PMID:28790198

    Open questions at the time
    • Binding site for 2′-deoxy-ADPR not structurally resolved
    • Relative physiological concentrations of ADPR vs. 2′-deoxy-ADPR in most tissues unknown
    • PYK2-TRPM2 physical interaction not demonstrated
  11. 2018 High

    Cryo-EM structures of zebrafish and human TRPM2 in multiple ligand-bound states revealed a two-step gating mechanism: ADPR binds the MHR1/2 cleft (not solely NUDT9-H), rotating MHR1/2 and disrupting intersubunit NUDT9-H contacts, while Ca2+ binding at a transmembrane site engages the TRP helix to open the lower gate.

    Evidence Single-particle cryo-EM at near-atomic resolution of zebrafish and human TRPM2 in apo, ADPR-bound, and ADPR+Ca2+-bound states; functional validation by electrophysiology

    PMID:30250252 PMID:30467180

    Open questions at the time
    • Open-state structure at true atomic resolution still lacking
    • CaM-binding domain and N-terminal gating contributions not resolved in structures
    • Mechanism of inactivation not captured
  12. 2019 High

    The evolutionary trajectory of TRPM2 was clarified: invertebrate TRPM2 retains active ADPRase catalysis in the Nudix domain, but this activity was lost in early vertebrate evolution concurrently with loss of pore stability, explaining why vertebrate NUDT9-H is vestigial for hydrolysis but critical for ligand-dependent gating.

    Evidence Comparative in vitro ADPRase assays with isolated domains from Nematostella, Salpingoeca, zebrafish, and human; patch-clamp of orthologues; pore mutagenesis

    PMID:30938679

    Open questions at the time
    • Selective pressure driving loss of catalysis not established
    • Whether vestigial NUDT9-H has any residual product release function unknown
  13. 2021 High

    Two new functional partnerships were defined: TRPM2 is ubiquitinated by the E3 ligase TRIM21 at K1218 (regulated by the antisense lncRNA TRPM2-AS), and TRPM2 functionally couples with CD36 to amplify oxLDL uptake and foam cell formation, promoting atherogenesis in macrophages.

    Evidence TRIM21-TRPM2 Co-IP, K1218 mutation, ubiquitination assays, lncRNA-immunoprecipitation; global and macrophage-specific TRPM2-KO in ApoE−/− atherosclerosis model with CD36 signaling assays

    PMID:33903714 PMID:35421327

    Open questions at the time
    • Whether TRIM21-mediated degradation is regulated by oxidative stress not tested
    • Structural basis of TRPM2-CD36 functional coupling unknown
  14. 2022 High

    TRPM2 was shown to physically associate with extrasynaptic NMDARs, promoting their surface expression and enhancing excitotoxic neuronal death during ischemia; a peptide disrupting this complex is neuroprotective in vivo.

    Evidence Co-immunoprecipitation of TRPM2-NMDAR complex; surface biotinylation; electrophysiology; therapeutic peptide in MCAO stroke model

    PMID:35421327

    Open questions at the time
    • Interaction interface between TRPM2 and specific NMDAR subunits not structurally defined
    • Whether TRPM2-NMDAR coupling occurs in non-neuronal cells unknown
  15. 2023 High

    Bilirubin was identified as a direct extracellular agonist of TRPM2, gating the channel independently of ADPR/Ca2+ through a specific cavity (D1066), establishing a new non-canonical activation mode that amplifies ischemic brain injury in a feed-forward loop; additionally, TRPM2-mediated Ca2+ was linked to ferroptosis via an MCU-ALOX12 axis in hepatic ischemia-reperfusion.

    Evidence D1066A knock-in mice; TRPM2-KO; electrophysiology with bilirubin; competitive binding assays; MCAO model; RNA-seq with ALOX12 upregulation; MCU-dependent mitochondrial Ca2+ measurement; ferroptosis assays in vivo

    PMID:36921602 PMID:37275121

    Open questions at the time
    • Bilirubin binding site not structurally resolved at atomic level
    • Whether bilirubin-TRPM2 signaling operates in non-neuronal tissues not tested
    • Relative contribution of ferroptosis vs. apoptosis in TRPM2-dependent cell death not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of CaM-dependent gating, the mechanism by which TRPM2 is differentially sorted to plasma membrane vs. lysosomes, how bilirubin and ADPR gating interact when both are present, and whether distinct downstream death programs (apoptosis, ferroptosis, necrosis) are independently tunable by different TRPM2 activation modes.
  • CaM-TRPM2 structural interface unresolved
  • Lysosomal vs. plasma membrane sorting mechanism unknown
  • Integrated model of multi-agonist gating lacking
  • Cell-type-specific wiring of downstream death programs not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 5 GO:0140299 molecular sensor activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005764 lysosome 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-382551 Transport of small molecules 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-168256 Immune System 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9612973 Autophagy 1
Partners
CAMCD36EFHC1GRIN2BRAC1TRIM21
Complex memberships
TRPM2 homotetramer

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 LTRPC2/TRPM2 contains a C-terminal NUDT9 homology domain that functions as an ADP-ribose pyrophosphatase; free ADP-ribose (ADPR) directly gates TRPM2 as a Ca2+-permeable cation channel, establishing ADPR as a novel intracellular second messenger for Ca2+ entry. Whole-cell and single-channel patch-clamp in HEK-293 cells expressing LTRPC2; biochemical identification of NUDT9 domain; native current recording in U937 monocytes Nature High 11385575
2001 Intracellular ADPR and NAD directly activate TRPM2 as a Ca2+-permeable nonselective cation channel in immunocytes; intracellular ATP suppresses this activation. Whole-cell patch-clamp and Ca2+ imaging in LTRPC2-expressing cells and native immunocytes Science High 11509734
2002 TRPM2 is activated by H2O2 and reactive oxygen/nitrogen species; sensitivity to redox-state modifiers is attributable to agonistic binding of NAD+ to the MutT (Nudix) motif; arachidonic acid and Ca2+ are positive regulators; TRPM2 activation confers susceptibility to cell death. Whole-cell patch-clamp, Ca2+ imaging, antisense oligonucleotide knockdown in HEK cells and native cells; H2O2 and TNFα treatment Molecular cell High 11804595
2002 A splice variant of TRPM2 lacking amino acids 1292–1325 (C-terminal deletion) found in neutrophils is activated by H2O2 but not by ADPR, demonstrating that H2O2-mediated activation is independent of the ADPR-binding Nudix domain. Whole-cell patch-clamp in HEK-293 cells expressing wild-type or splice variant TRPM2; Ca2+ imaging; identification of splice variant by molecular cloning The Journal of biological chemistry High 11960981
2003 A short isoform of TRPM2 (TRPM2-S), arising from alternative splicing that removes the four C-terminal transmembrane domains and pore region, localizes to the plasma membrane and directly interacts with full-length TRPM2-L (shown by co-immunoprecipitation); co-expression of TRPM2-S suppresses H2O2-induced Ca2+ influx through TRPM2-L and inhibits cell death, functioning as a dominant negative. Co-immunoprecipitation, confocal microscopy for localization, Ca2+ influx assay, cell death/apoptosis assay in HEK 293T cells The Journal of biological chemistry High 12594222
2005 TRPM2 activation by oxidative stress or TNFα mediates cell death through increased intracellular Ca2+, followed by activation of caspases-8, -9, -3, -7 and PARP cleavage; chelation of intracellular Ca2+ with BAPTA blocked caspase/PARP cleavage and cell death, demonstrating Ca2+ is the critical intermediary. Retroviral overexpression/knockdown of TRPM2 isoforms in U937 cells; Ca2+ chelation; caspase/PARP western blot; viability and apoptosis assays American journal of physiology. Cell physiology High 16306129
2006 Cyclic ADP-ribose (cADPR) and NAADP strongly activate natively expressed TRPM2 channels in Jurkat T cells; their activity is partially suppressed by the ADPR antagonist AMP and fully suppressed by 8-Br-cADPR, suggesting cADPR and NAADP share a common binding site on TRPM2 that acts synergistically with ADPR. Patch-clamp electrophysiology in Jurkat T cells; pharmacological antagonism with AMP and 8-Br-cADPR FASEB journal Medium 16585058
2007 TRPM2 mediates H2O2-induced Ca2+ entry and increased endothelial permeability through an ADP-ribose–dependent mechanism; H2O2 stimulates ADPR formation, which opens TRPM2; siRNA depletion or dominant-negative TRPM2-S expression inhibited the cationic current, Ca2+ entry, and transendothelial electrical resistance decrease. Patch-clamp recording, fura-2 Ca2+ imaging, transendothelial electrical resistance measurement, siRNA knockdown, overexpression in endothelial cells Circulation research High 18048770
2009 Intracellular Ca2+ activates TRPM2 via a calmodulin (CaM)-binding domain in the N-terminus, independent of ADPR-binding sites; Ca2+-mediated gating is the only known activator of ADPR-insensitive splice isoforms; both intracellular Ca2+ release and receptor-activation-induced Ca2+ release can activate endogenous TRPM2 in intact cells. Whole-cell patch-clamp, Ca2+ imaging, mutagenesis of ADPR-binding sites, CaM-binding domain identification, intact cell activation assays Proceedings of the National Academy of Sciences of the United States of America High 19372375
2011 TRPM2 in dendritic cells localizes to endolysosomal vesicles (not the plasma membrane) and functions as a Ca2+ release channel from lysosomes, contributing to DC chemotaxis; TRPM2-deficient DCs show impaired maturation and directional migration in response to chemokines. siRNA knockdown and TRPM2-knockout mice; endolysosomal localization by confocal immunofluorescence; Ca2+ signaling assays; in vitro and in vivo chemotaxis assays FASEB journal High 21753080
2012 EFHC1 (mutated in juvenile myoclonic epilepsy) physically interacts with both N- and C-terminal cytoplasmic regions of TRPM2 (shown by co-immunoprecipitation) and potentiates H2O2- and ADPR-induced Ca2+ responses and cationic currents through TRPM2; JME mutations in EFHC1 reverse this potentiation. Co-immunoprecipitation, whole-cell patch-clamp, Ca2+ imaging in HEK293 cells; in situ hybridization for co-expression Cell calcium Medium 22226147
2013 TRPM2 deficiency in mice modulates NMDAR subunit composition: TRPM2-null neurons upregulate GluN2A-containing NMDARs and downregulate GluN2B-containing NMDARs, augmenting prosurvival Akt/ERK signaling and inhibiting GSK3β, resulting in reduced ischemic infarct volume. TRPM2-knockout mice; middle cerebral artery occlusion model; field potential electrophysiology in brain slices; western blot for signaling proteins; pharmacological NMDAR subunit inhibitors The Journal of neuroscience Medium 24174660
2013 TRPM2 channels mediate ischemic kidney injury through RAC1 activation: TRPM2 promotes RAC1 activation after ischemia; active RAC1 physically interacts with TRPM2 and increases TRPM2 plasma membrane expression, creating a positive feedback loop that amplifies NADPH oxidase activity and oxidative stress. TRPM2-knockout mice; chimeric mouse models; Co-IP of active RAC1 with TRPM2; pharmacological RAC1 inhibition in vivo; NADPH oxidase activity assays The Journal of clinical investigation High 25295536
2015 TRPM2-mediated Ca2+ influx is required to maintain cardiac myocyte mitochondrial function and protect against hypoxia-reoxygenation injury; loss-of-function TRPM2 mutants (E960D, P1018L) fail to reduce mitochondrial ROS in knockout myocytes, demonstrating Ca2+ entry (not reverse NCX) is the operative mechanism. Adenoviral rescue with WT and loss-of-function TRPM2 mutants in global TRPM2-KO hearts; mitochondrial superoxide measurements; oxygen consumption rate; cardiac-specific TRPM2-KO in ischemia-reperfusion American journal of physiology. Heart and circulatory physiology High 25576627
2015 TRPM2 activation by H2O2 induces intracellular Ca2+ and Zn2+ elevation in pancreatic β-cells; Zn2+ originates from TRPM2-expressing lysosomes, and Ca2+-potentiated Zn2+ release (not Ca2+ alone) is primarily responsible for apoptotic β-cell death; TRPM2-KO mice are protected from streptozotocin-induced β-cell death. Zn2+ chelation experiments, lysosomal TRPM2 localization, Ca2+ and Zn2+ imaging, TRPM2-KO mouse model, INS1 and HEK293 cells, isolated islets The Biochemical journal High 25562606
2015 TRPM2 activation by oxidative stress regulates GSK-3 phosphorylation in brain via calcineurin: TRPM2 activation leads to Ca2+-dependent calcineurin activation, which dephosphorylates GSK-3; the bipolar disorder-associated D543E loss-of-function TRPM2 mutant fails to dephosphorylate GSK-3, and TRPM2-KO mice show increased GSK-3 phosphorylation and BD-like behavior. TRPM2-KO mice; overexpression of WT and D543E mutant; calcineurin inhibitor experiments; western blot for p-GSK-3; behavioral assays; EEG recordings The Journal of neuroscience High 26311765
2016 Oxidative stress activates a TRPM2-Ca2+-CAMK2-BECN1 signaling cascade to inhibit autophagy: TRPM2-mediated Ca2+ influx activates CAMK2 (by phosphorylation and oxidation), which phosphorylates BECN1/Beclin-1 at Ser295, reducing BECN1–PIK3C3 association while increasing BECN1–BCL2 binding, thereby blocking early autophagy induction. Pharmacological TRPM2 inhibition and KO; CAMK2 phosphorylation/oxidation assays; BECN1 co-immunoprecipitation with PIK3C3 and BCL2; site-directed mutagenesis of Ser295; autophagy flux assays; validated in acetaminophen liver injury model Autophagy High 27245989
2017 2'-Deoxy-ADPR is an endogenous TRPM2 superagonist producing 10.4-fold higher whole-cell currents than ADPR at saturation, due to decreased inactivation rate and higher open probability; 2'-deoxy-ADPR is synthesized endogenously by NMNAT-2 and CD38 acting sequentially on NMN and 2'-deoxy-ATP, and was detected in Jurkat T cells by HPLC/mass spectrometry. Whole-cell patch-clamp; single-channel analysis; HPLC and mass spectrometry detection of endogenous 2'-deoxy-ADPR; in vitro enzymatic synthesis assay with NMNAT-2 and CD38 Nature chemical biology High 28671679
2017 TRPM2 channel activation by Zn2+ in microglia requires a PKC/NADPH oxidase-mediated ROS generation and PARP-1 stimulation pathway; subsequently, TRPM2-mediated Ca2+ entry triggers a PYK2/MEK/ERK positive feedback mechanism that amplifies further TRPM2 activation, driving Ca2+ overload and cell death. TRPM2-KO microglia; pharmacological inhibitors of PKC (chelerythrine), NOX (DPI, GKT137831, Phox-I2), PARP (PJ34, DPQ), PYK2 (PF431396), MEK/ERK (U0126); Ca2+ imaging; cell death assays Scientific reports Medium 28322340
2017 Neutrophil-derived reactive oxygen species activate TRPM2 in endothelial cells through ADPR generation (requiring PARP); TRPM2-mediated Ca2+ entry triggers VE-cadherin phosphorylation, adherens junction disassembly, and transendothelial neutrophil migration; conditional EC-specific TRPM2 deletion prevents PMN transmigration in LPS-challenged mice. Conditional EC-specific TRPM2 knockout mice; gp91phox-/- PMNs; ADPR-insensitive TRPM2 mutant (C1008A) overexpression; PARP silencing; Ca2+ entry and VE-cadherin phosphorylation assays; in vivo PMN transmigration Circulation research High 28790198
2017 Ligand-induced TRPM2 activation critically depends on hydrogen bonding of Arg1433 and Tyr1349 in the NUDT9H domain with the terminal ribose of ADPR; all ADPR derivatives modified at the terminal ribose abolished agonist activity; these residues were identified by structure-guided mutagenesis combined with synthetic ADPR analogues. Site-directed mutagenesis of NUDT9H domain; patch-clamp electrophysiology in TRPM2-expressing HEK293 cells; synthetic ADPR analogue library; structure-activity relationship analysis The Biochemical journal High 28515263
2017 Palmitate-induced β-cell death involves TRPM2-mediated rise in mitochondrial Zn2+, which drives Drp-1 recruitment to mitochondria, mitochondrial fission and membrane potential loss; Zn2+ chelation alone prevents fission, and TRPM2 inhibition/KO prevents palmitate-induced fission in rodent and human islets. TRPM2 inhibition, RNAi silencing, and KO; mitochondrial Zn2+ and Ca2+ imaging; Drp-1 recruitment assay; membrane potential measurement; INS1 cells, mouse and human islets Cell death and differentiation High 28753206
2018 Cryo-EM structures of zebrafish TRPM2 in apo/closed and ADPR+Ca2+-bound/open states reveal that ADPR binds to a bi-lobed MHR1/2 domain (not exclusively NUDT9-H), and that NUDT9-H domains hang beneath MHR1/2; Ca2+ binding in the transmembrane region, together with ADPR at MHR1/2, is required for channel opening. Single-particle cryo-electron microscopy at near-atomic resolution; functional validation by electrophysiology Nature High 30250252
2018 Cryo-EM structures of human TRPM2 alone, with ADPR, and with ADPR+Ca2+ reveal the gating mechanism: NUDT9H forms intra- and intersubunit interactions with MHR1/2/3 in the apo state; ADPR binding causes MHR1/2 rotation and disrupts intersubunit interactions; Ca2+ binding further engages transmembrane helices and the TRP helix to open the lower gate. Single-particle cryo-electron microscopy of human TRPM2 in three states; structural comparison; functional electrophysiology Science High 30467180
2019 TRPM2 Nudix motifs are canonical (enzymatically active ADPRases) in invertebrates but vestigial (inactive) in vertebrates; invertebrate TRPM2 (from Nematostella and Salpingoeca) possesses active ADPR phosphohydrolase activity; loss of ADPRase activity and loss of pore stability (inactivation) co-occurred in early vertebrate TRPM2 evolution. Comparative sequence analysis; in vitro ADPRase activity assays with isolated domains; whole-cell patch-clamp of TRPM2 orthologues (nvTRPM2, srTRPM2, drTRPM2, hsTRPM2); pore sequence mutagenesis eLife High 30938679
2020 In dendritic cells, TRPM2 is required for NLRP3 inflammasome activation in response to ROS; TRPM2-mediated Ca2+ permeation links oxidative stress sensing to NLRP3 activation. TRPM2-KO macrophages/DCs; NLRP3 inflammasome activation assays; Ca2+ imaging; cytokine secretion (IL-1β); ROS measurements (review synthesizing experimental findings) Current opinion in immunology Medium 32058297
2021 TRPM2 promotes atherogenesis through a TRPM2-CD36 axis: oxLDL activates CD36, which induces TRPM2 channel activity, and conversely TRPM2 promotes CD36 signaling; macrophage-specific or global Trpm2 deletion protects ApoE-/- mice from atherosclerosis by reducing oxLDL uptake, foam cell formation, and macrophage infiltration. Global and macrophage-specific Trpm2-KO in ApoE-/- atherosclerosis model; oxLDL and thrombospondin-1 stimulation assays; TRPM2 current recordings; CD36 signaling assays in KO and WT macrophages Nature cardiovascular research High 35421327
2022 TRPM2 physically associates with extrasynaptic NMDARs; this TRPM2-NMDAR complex promotes surface expression of extrasynaptic NMDARs and enhances NMDAR-mediated excitotoxicity during ischemia; a membrane-permeable peptide targeting the NMDAR-interacting motif on TRPM2 disrupts the complex and protects neurons in vitro and in vivo. Co-immunoprecipitation of TRPM2-NMDAR complex; surface biotinylation assays for NMDAR expression; electrophysiology; cell death assays; in vivo MCAO stroke model with therapeutic peptide Neuron High 35421327
2023 Bilirubin acts as a direct extracellular agonist of TRPM2, gating the channel independently of canonical intracellular agonists (ADPR/Ca2+) by binding to a specific cavity; a knock-in loss-of-binding mutation (D1066A) antagonizes ischemic neurotoxicity; ischemic insults induce endogenous bilirubin release, creating a vicious cycle of TRPM2-mediated Ca2+-dependent brain injury. TRPM2-knockout mice; TRPM2 antagonist A23; D1066A knock-in mice; electrophysiology with bilirubin application; competitive binding assays; MCAO stroke model Neuron High 36921602
2021 TRPM2 protein is ubiquitinated by the E3 ligase TRIM21 at K1218; lncTRPM2-AS (a non-coding antisense RNA from the same locus) blocks TRIM21-mediated TRPM2 ubiquitination and degradation, maintaining TRPM2 protein levels and intracellular calcium signaling in macrophages. RNA-immunoprecipitation, mass spectrometry, Co-IP of TRIM21 with TRPM2, ubiquitination assays, K1218 mutation analysis, intracellular calcium measurement Cell death & disease Medium 33903714
2023 TRPM2-mediated Ca2+ influx promotes hepatic ischemia-reperfusion ferroptosis via Ca2+-induced mitochondrial Ca2+ accumulation (through the mitochondrial uniporter MCU) and upregulation of ALOX12, leading to mitochondrial lipid peroxidation; TRPM2 inhibition or Ca2+ depletion relieved ferroptosis in vitro and in vivo. TRPM2-KO mice; RNA sequencing; ALOX12 expression analysis; MCU-dependent mitochondrial Ca2+ measurement; ferroptosis assays; TRPM2 inhibitor treatment in vivo Research (Washington, D.C.) Medium 37275121

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Biological insights from 108 schizophrenia-associated genetic loci. Nature 5878 25056061
2013 Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. Nature genetics 3440 24162737
2009 Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nature genetics 2302 19734902
2009 Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nature genetics 2003 19734903
2011 Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature genetics 1562 21460841
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2010 Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 992 20460622
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2001 ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 782 11385575
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2016 TREM2 Binds to Apolipoproteins, Including APOE and CLU/APOJ, and Thereby Facilitates Uptake of Amyloid-Beta by Microglia. Neuron 724 27477018
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2002 LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Molecular cell 682 11804595
2004 The human plasma proteome: a nonredundant list developed by combination of four separate sources. Molecular & cellular proteomics : MCP 658 14718574
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 616 14630798
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2002 Clusterin. The international journal of biochemistry & cell biology 454 11906815
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2001 Immunocyte Ca2+ influx system mediated by LTRPC2. Science (New York, N.Y.) 389 11509734
1999 Clusterin has chaperone-like activity similar to that of small heat shock proteins. The Journal of biological chemistry 389 10066740
1989 Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid. Proceedings of the National Academy of Sciences of the United States of America 389 2780565
2005 Clusterin inhibits apoptosis by interacting with activated Bax. Nature cell biology 382 16113678
2010 Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypes. Archives of neurology 354 20697030
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
2002 Activation of the cation channel long transient receptor potential channel 2 (LTRPC2) by hydrogen peroxide. A splice variant reveals a mode of activation independent of ADP-ribose. The Journal of biological chemistry 299 11960981
2003 A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death. The Journal of biological chemistry 202 12594222
2007 Role of TRPM2 channel in mediating H2O2-induced Ca2+ entry and endothelial hyperpermeability. Circulation research 191 18048770
2018 Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. Nature 152 30250252
2006 Nicotinic acid adenine dinucleotide phosphate and cyclic ADP-ribose regulate TRPM2 channels in T lymphocytes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 148 16585058
2018 Structures and gating mechanism of human TRPM2. Science (New York, N.Y.) 146 30467180
2011 Roles of TRPM2 in oxidative stress. Cell calcium 137 21616534
2003 TRPM2 Ca2+ permeable cation channels: from gene to biological function. Cell calcium 136 12765697
2009 Intracellular calcium activates TRPM2 and its alternative spliced isoforms. Proceedings of the National Academy of Sciences of the United States of America 127 19372375
2011 Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ release. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 124 21753080
2010 TRPM2 cation channels, oxidative stress and neurological diseases: where are we now? Neurochemical research 124 21140288
2013 The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation. Immunologic research 117 22975787
2019 TRPM2 in Cancer. Cell calcium 107 30925291
2005 TRPM2 is an ion channel that modulates hematopoietic cell death through activation of caspases and PARP cleavage. American journal of physiology. Cell physiology 106 16306129
2014 TRPM2 mediates ischemic kidney injury and oxidant stress through RAC1. The Journal of clinical investigation 104 25295536
2020 TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions. Redox biology 102 33130440
2005 TRPM2: a calcium influx pathway regulated by oxidative stress and the novel second messenger ADP-ribose. Pflugers Archiv : European journal of physiology 94 15952035
2016 Mechanistic study of TRPM2-Ca(2+)-CAMK2-BECN1 signaling in oxidative stress-induced autophagy inhibition. Autophagy 89 27245989
2013 Modulation of NMDAR subunit expression by TRPM2 channels regulates neuronal vulnerability to ischemic cell death. The Journal of neuroscience : the official journal of the Society for Neuroscience 89 24174660
2022 Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury. Neuron 86 35421327
2016 TRPM2 Promotes Neurotoxin MPP+/MPTP-Induced Cell Death. Molecular neurobiology 86 27957685
2020 TRPM2, linking oxidative stress and Ca2+ permeation to NLRP3 inflammasome activation. Current opinion in immunology 82 32058297
2010 TRPM2 channel properties, functions and therapeutic potentials. Expert opinion on therapeutic targets 82 20670202
2020 Resveratrol attenuates hypoxia-induced neuronal cell death, inflammation and mitochondrial oxidative stress by modulation of TRPM2 channel. Scientific reports 81 32296107
2007 TRPM7 and TRPM2-Candidate susceptibility genes for Western Pacific ALS and PD? Biochimica et biophysica acta 70 17395433
2016 TRPM2 ion channels regulate macrophage polarization and gastric inflammation during Helicobacter pylori infection. Mucosal immunology 69 27435104
2017 2'-Deoxyadenosine 5'-diphosphoribose is an endogenous TRPM2 superagonist. Nature chemical biology 67 28671679
2017 Neutrophil Activation of Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration and Vascular Injury. Circulation research 67 28790198
2014 TRPM2. Handbook of experimental pharmacology 66 24756715
2013 Androgen and PARP-1 regulation of TRPM2 channels after ischemic injury. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 66 23801245
2021 TRPM2 promotes pancreatic cancer by PKC/MAPK pathway. Cell death & disease 62 34099637
2013 Role of TRPM2 in cell proliferation and susceptibility to oxidative stress. American journal of physiology. Cell physiology 60 23302782
2021 Role of TRPM2 in brain tumours and potential as a drug target. Acta pharmacologica Sinica 59 34108651
2013 Structure-activity relationship of adenosine 5'-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: rational design of antagonists. Journal of medicinal chemistry 58 24304219
2017 Signalling mechanisms mediating Zn2+-induced TRPM2 channel activation and cell death in microglial cells. Scientific reports 57 28322340
2017 Involvement of TRPM2 and TRPV1 channels on hyperalgesia, apoptosis and oxidative stress in rat fibromyalgia model: Protective role of selenium. Scientific reports 57 29235496
2015 Ca²⁺ entry via Trpm2 is essential for cardiac myocyte bioenergetics maintenance. American journal of physiology. Heart and circulatory physiology 57 25576627
2023 TRPM2 Mediates Hepatic Ischemia-Reperfusion Injury via Ca2+-Induced Mitochondrial Lipid Peroxidation through Increasing ALOX12 Expression. Research (Washington, D.C.) 55 37275121
2020 Deficiency of TRPM2 leads to embryonic neurogenesis defects in hyperthermia. Science advances 55 31911949
2019 TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway. Scientific reports 55 30862883
2007 TRPM2. Handbook of experimental pharmacology 55 17217061
2015 TRPM2, a Susceptibility Gene for Bipolar Disorder, Regulates Glycogen Synthase Kinase-3 Activity in the Brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 26311765
2023 TRPM2 protects against cisplatin-induced acute kidney injury and mitochondrial dysfunction via modulating autophagy. Theranostics 53 37649595
2015 TRPM2 protects against tissue damage following oxidative stress and ischaemia-reperfusion. The Journal of physiology 53 26420388
2019 Curcumin enhances cisplatin-induced human laryngeal squamous cancer cell death through activation of TRPM2 channel and mitochondrial oxidative stress. Scientific reports 52 31780732
2017 Transient receptor potential melastatin 2 channels (TRPM2) mediate neonatal hypoxic-ischemic brain injury in mice. Experimental neurology 50 28668375
2010 Chemical physiology of oxidative stress-activated TRPM2 and TRPC5 channels. Progress in biophysics and molecular biology 49 20553742
2005 Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones. Neuropharmacology 48 16260005
2024 Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway. Molecular cancer 46 38532427
2015 TRPM2-mediated intracellular Zn2+ release triggers pancreatic β-cell death. The Biochemical journal 45 25562606
2018 Hyperosmotic Stress-Induced TRPM2 Channel Activation Stimulates NLRP3 Inflammasome Activity in Primary Human Corneal Epithelial Cells. Investigative ophthalmology & visual science 44 29971445
2022 A novel antagonist of TRPM2 and TRPV4 channels: Carvacrol. Metabolic brain disease 43 34989943
2020 Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mitochondrial oxidative stress, and apoptosis in microglia. Metabolic brain disease 43 33044639
2019 TRPM2-AS promotes cancer cell proliferation through control of TAF15. The international journal of biochemistry & cell biology 43 31887411
2014 The role of TRPM2 in pancreatic β-cells and the development of diabetes. Cell calcium 42 25084624
2017 TRPM2-mediated rise in mitochondrial Zn2+ promotes palmitate-induced mitochondrial fission and pancreatic β-cell death in rodents. Cell death and differentiation 41 28753206
2016 The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma. Scientific reports 41 28008929
2018 8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury. Journal of cellular physiology 40 30191993
2005 TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors. Pflugers Archiv : European journal of physiology 40 16001276
2022 TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages. Nature cardiovascular research 38 35445217
2012 The juvenile myoclonic epilepsy-related protein EFHC1 interacts with the redox-sensitive TRPM2 channel linked to cell death. Cell calcium 37 22226147
2011 Expression and functional properties of TRPM2 channels in dopaminergic neurons of the substantia nigra of the rat. Journal of neurophysiology 37 21900507
2017 Ligand-induced activation of human TRPM2 requires the terminal ribose of ADPR and involves Arg1433 and Tyr1349. The Biochemical journal 36 28515263
2023 Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage. Neuron 35 36921602
2005 Regulation of TRPM2 channels in neutrophil granulocytes by ADP-ribose: a promising pharmacological target. Naunyn-Schmiedeberg's archives of pharmacology 35 15841395
2018 TRPM2 in the Brain: Role in Health and Disease. Cells 33 30037128
2017 Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues. Chemical biology & drug design 33 29034580
2013 Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage. Biochimica et biophysica acta 33 23458684
2019 Suppression of TRPM2 reduces renal fibrosis and inflammation through blocking TGF-β1-regulated JNK activation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 31655312
2018 TRPM2 promotes the proliferation and invasion of pancreatic ductal adenocarcinoma. Molecular medicine reports 32 29620272
2016 ADP-Ribose Activates the TRPM2 Channel from the Sea Anemone Nematostella vectensis Independently of the NUDT9H Domain. PloS one 31 27333281
2019 TRPM2 mediates distruption of autophagy machinery and correlates with the grade level in prostate cancer. Journal of cancer research and clinical oncology 30 30888515
2019 Pharmacology of JNJ-28583113: A novel TRPM2 antagonist. European journal of pharmacology 30 30965058
2016 Glia and TRPM2 Channels in Plasticity of Central Nervous System and Alzheimer's Diseases. Neural plasticity 30 26942016
2021 Reactive Oxygen Species-Induced TRPM2-Mediated Ca2+ Signalling in Endothelial Cells. Antioxidants (Basel, Switzerland) 29 34063677
2017 TRPM2 contributes to LPC-induced intracellular Ca2+ influx and microglial activation. Biochemical and biophysical research communications 29 28223219
2021 LncTRPM2-AS inhibits TRIM21-mediated TRPM2 ubiquitination and prevents autophagy-induced apoptosis of macrophages in asthma. Cell death & disease 28 34903714
2018 Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca2+-dependent CaMKII/JNK cascade. Metabolism: clinical and experimental 28 29775644
2021 TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention. Channels (Austin, Tex.) 27 33455532
2020 TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis. The Journal of physiology 27 31917868
2016 Role of transient receptor potential melastatin 2 (TRPM2) channels in visceral nociception and hypersensitivity. Experimental neurology 27 27616276
2023 Trpm2 deficiency in microglia attenuates neuroinflammation during epileptogenesis by upregulating autophagy via the AMPK/mTOR pathway. Neurobiology of disease 26 37648036
2021 LncRNA TRPM2-AS promotes ovarian cancer progression and cisplatin resistance by sponging miR-138-5p to release SDC3 mRNA. Aging 26 33621194
2021 Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel. Life (Basel, Switzerland) 26 33925466
2018 Nociceptive Roles of TRPM2 Ion Channel in Pathologic Pain. Molecular neurobiology 26 29327205
2024 Activation of endothelial TRPM2 exacerbates blood-brain barrier degradation in ischemic stroke. Cardiovascular research 25 37595268
2024 Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury. Frontiers in immunology 25 39007141
2021 The Role of TRPM2 in Endothelial Function and Dysfunction. International journal of molecular sciences 25 34299254
2016 Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2. Acta physiologica (Oxford, England) 25 28028935
2019 Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates. eLife 24 30938679
2014 Inhibitory effects of AG490 on H2O2-induced TRPM2-mediated Ca(2+) entry. European journal of pharmacology 24 25179574
2009 In with the TRP channels: intracellular functions for TRPM1 and TRPM2. Science signaling 24 19887679
2022 Down-regulation of TRPM2 attenuates hepatic ischemia/reperfusion injury through activation of autophagy and inhibition of NLRP3 inflammasome pathway. International immunopharmacology 23 35021129
2019 TRPM2-AS inhibits the growth, migration, and invasion of gliomas through JNK, c-Jun, and RGS4. Journal of cellular physiology 23 31637708
2024 LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis. Cellular & molecular biology letters 22 38956502
2023 Modulating mitochondrial calcium channels (TRPM2/MCU/NCX) as a therapeutic strategy for neurodegenerative disorders. Frontiers in neuroscience 22 37928737
2020 Ethanol Induces Microglial Cell Death via the NOX/ROS/PARP/TRPM2 Signalling Pathway. Antioxidants (Basel, Switzerland) 22 33317056