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Showing FOLH1 — GCP2 is a alias.

FOLH1

Glutamate carboxypeptidase 2 · UniProt Q04609

Length
750 aa
Mass
84.3 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 17 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOLH1 (PSMA/GCPII/NAALADase) is a membrane-bound glutamate-preferring carboxypeptidase with two reconstituted enzymatic activities: NAALADase, which hydrolyzes the neuropeptide NAAG to release glutamate, and gamma-glutamyl carboxypeptidase (folate hydrolase) activity (PMID:11210180). The brain NAALADase and prostate PSMA are products of the same gene, sharing a common splice form, kinetic profile, and immunoreactivity (PMID:9694964). In the central nervous system the enzyme localizes to neuropil where it co-localizes with its NAAG substrate, and it is also present in the brush border of renal proximal tubules (PMID:1545010); in vivo it controls the balance between extracellular glutamate and NAAG, as pharmacological inhibition lowers glutamate and raises NAAG during ischemia (PMID:10668445), and genetic deletion reduces excitotoxic glutamate and neuronal damage after traumatic brain injury, an effect not compensated by the paralog GCPIII (PMID:37349952). FOLH1 genotype tunes synaptic NAAG concentration and cognitive performance in humans (PMID:33256444), and its enzymatic activity is elevated in inflamed intestinal mucosa, where genetic or pharmacological abrogation ameliorates colitis (PMID:27536732). Prostate-restricted expression of the human gene is driven by an intronic enhancer (PSME) that is intrinsically prostate-specific and repressed by androgen (PMID:11350116, PMID:34299051), directly silenced by Sox7 binding (PMID:30488457), and epigenetically controlled via CpG methylation and H3K27 acetylation at the locus (PMID:36821396). At the protein level, filamin A binds the cytoplasmic tail to slow clathrin-mediated internalization and dampen NAALADase activity (PMID:12750292), and a splice variant, PSM-E, suppresses prostate cancer metastasis by recruiting RACK1 to inhibit macrophage M2 polarization through FAK/ERK signaling (PMID:39538297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 Medium

    Established that NAALADase is a membrane enzyme acting on NAAG in situ, placing it within glutamatergic neurotransmission rather than as a bystander activity.

    Evidence Immunocytochemistry co-localizing NAALADase-IR with NAAG-IR in rat brain neuropil and kidney brush border

    PMID:1545010

    Open questions at the time
    • Single immunolocalization method
    • Did not establish molecular identity with prostate PSMA
  2. 1998 High

    Resolved whether brain NAALADase and prostate PSMA are distinct proteins by showing they are products of the same gene sharing a common mRNA splice form.

    Evidence Kinetic/pharmacological comparison, Northern blot, immunoprecipitation with anti-PSMA mAb, and RT-PCR cloning

    PMID:9694964

    Open questions at the time
    • Did not address tissue-specific transcriptional control
    • Functional consequences in each tissue not separated
  3. 2001 High

    Reconstituted the dual enzymatic identity of FOLH1 by direct transfection, confirming both NAALADase and folate hydrolase activities reside in one gene product.

    Evidence cDNA cloning, transfection, NAALADase and folate hydrolase assays, RT-PCR tissue profiling in mouse Folh1

    PMID:11210180

    Open questions at the time
    • Mouse lacks prostate expression, limiting model fidelity for human prostate biology
    • Substrate hierarchy in vivo not defined
  4. 2001 High

    Mapped the cis-regulatory basis of prostate-specific expression to an intronic enhancer (PSME) carrying both tissue specificity and androgen repression.

    Evidence Enhancer trap and luciferase reporter assays in prostate vs non-prostate cell lines with androgen treatment

    PMID:11350116

    Open questions at the time
    • Trans-acting factors binding PSME not yet identified
    • Mechanism of androgen repression unresolved
  5. 2001 Medium

    Demonstrated in vivo that FOLH1 activity governs the extracellular glutamate/NAAG balance and that inhibition is neuroprotective via a glia- and mGluR-dependent route.

    Evidence Rat MCAO microdialysis with 2-PMPA; neuronal/glial co-culture pharmacology with selective mGlu receptor antagonists

    PMID:10668445 PMID:11525768

    Open questions at the time
    • Single-lab pharmacology
    • Direct enzymatic measurement of GCPII not coupled to receptor epistasis in same system
  6. 2003 High

    Identified post-translational regulation of PSMA trafficking and activity through cytoplasmic-tail binding of filamin A.

    Evidence Co-IP and reciprocal functional rescue in filamin-negative vs positive cell lines with internalization and enzymatic assays

    PMID:12750292

    Open questions at the time
    • Structural basis of tail-filamin interaction not defined
    • Physiological context of internalization control unclear
  7. 2016 High

    Extended FOLH1 pathophysiology beyond brain and prostate by linking its enzymatic activity to intestinal inflammation with genetic and pharmacological causal evidence.

    Evidence Human IBD specimen activity assays; FOLH1 KO and 2-PMPA inhibition in DSS and IL-10-/- colitis models

    PMID:27536732

    Open questions at the time
    • Substrate/metabolite driving colitis effect not pinpointed
    • Cell type responsible for elevated activity not defined
  8. 2016 Medium

    Showed PSMA expression can be induced de novo on tumor-associated neovascular endothelium, broadening its relevance as a targetable antigen.

    Evidence Cancer-conditioned media induction of PSMA in HUVECs in vitro and in co-implantation model with functional internalization of anti-PSMA mAb and nanoparticles

    PMID:27458033

    Open questions at the time
    • Inducing factor in conditioned media unidentified
    • Single-lab finding
  9. 2018 High

    Identified Sox7 as a direct transcriptional repressor of PSMA acting through defined SOX sites in the PSME enhancer.

    Evidence ChIP, EMSA, reporter assays, and stable Sox7 overexpression with domain mutants in prostate cancer cells

    PMID:30488457

    Open questions at the time
    • Upstream control of Sox7 in prostate cancer unclear
    • Interplay with androgen repression not integrated
  10. 2020 Medium

    Connected FOLH1 genetic variation to synaptic NAAG levels and human cognition, establishing functional consequence of the locus in vivo.

    Evidence rs202676 genotyping with DLPFC mRNA, 7-T MRS NAAG measurement, cognitive testing, and working-memory fMRI

    PMID:33256444

    Open questions at the time
    • Association rather than direct causal manipulation in humans
    • Mechanism linking mRNA increase to NAAG decrease inferred
  11. 2021 Medium

    Confirmed androgen receptor signaling negatively regulates PSMA, defining a therapeutically actionable axis (enzalutamide-induced PSMA upregulation).

    Evidence Enzalutamide treatment of multiple cell lines and xenografts with flow cytometry, IHC, and 68Ga-PSMA PET/CT

    PMID:34299051

    Open questions at the time
    • Single-lab study
    • Direct link to PSME enhancer occupancy not shown
  12. 2023 High

    Defined the epigenetic basis of PSMA loss in metastatic castration-resistant prostate cancer and showed it is pharmacologically reversible.

    Evidence Autopsy cohort profiling, H3K27ac ChIP, bisulfite methylation analysis, and HDAC inhibitor rescue in vitro and in vivo

    PMID:36821396

    Open questions at the time
    • Writer/eraser enzymes specific to the locus not identified
    • Durability of HDACi-restored expression unknown
  13. 2023 High

    Demonstrated GCPII-specific, GCPIII-independent control of excitotoxic glutamate and neuronal injury after traumatic brain injury via clean genetic epistasis.

    Evidence CRISPR/Cas9 single and double GCPII/GCPIII knockout mice in controlled cortical impact TBI with injury signaling and cognitive readouts

    PMID:37349952

    Open questions at the time
    • Cellular source of pathogenic glutamate not localized
    • Translation to pharmacological timing windows unaddressed
  14. 2024 Medium

    Assigned a tumor-suppressive signaling function to the PSM-E splice variant through RACK1 recruitment and macrophage repolarization.

    Evidence Co-IP with domain-mapping, IHC, and in vitro/in vivo PCa tumorigenesis models

    PMID:39538297

    Open questions at the time
    • Single-lab finding
    • Reciprocal validation and structural detail of RACK1 interaction limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the enzyme's catalytic activity is mechanistically coupled to its non-catalytic signaling roles (filamin trafficking, PSM-E/RACK1 immune modulation) and whether they operate independently of NAAG/folate hydrolysis remains unresolved.
  • No structural model linking ectodomain catalysis to cytoplasmic-tail signaling
  • Relative in vivo contribution of NAALADase vs folate hydrolase activities across tissues 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 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1643685 Disease 3 R-HSA-1430728 Metabolism 1
Partners
FLNARACK1SOX7

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Filamin A, an actin cross-linking protein, associates with the cytoplasmic tail of PSMA (FOLH1). This association localizes PSMA to the recycling endosomal compartment, reduces its internalization rate, and decreases its NAALADase enzymatic activity. Ectopic expression of PSMA in filamin-negative and filamin-positive cell lines; co-immunoprecipitation; functional internalization and enzymatic activity assays Cancer research High 12750292
2001 The PSMA gene (FOLH1) contains a tissue-specific enhancer (PSME) located in the third intron (~12 kb downstream from the transcription start site). PSME drives prostate-specific transcription (>250-fold activation in LNCaP cells) and is repressed by androgen, recapitulating androgen regulation of the endogenous FOLH1 gene. Both cell-type specificity and androgen regulation are intrinsic to the enhancer. Enhancer trap assay with overlapping DNA fragments; luciferase reporter assays in prostate and non-prostate cell lines; androgen treatment experiments Genomics High 11350116
2001 Mouse Folh1 (homolog of human PSMA/FOLH1) encodes a glutamate-preferring carboxypeptidase with two enzymatic activities: NAALADase (cleaves NAAG to release glutamate) and gamma-glutamyl carboxypeptidase (folate hydrolase). Cells transfected with Folh1 gained both NAALADase and folate hydrolase activities. Unlike human PSMA, mouse Folh1 is not expressed in the prostate but is expressed primarily in brain and kidney. cDNA cloning and transfection; NAALADase and folate hydrolase enzymatic activity assays; RT-PCR tissue expression profiling; FISH chromosomal mapping Mammalian genome High 11210180
1998 Human brain NAALADase and prostate PSMA (FOLH1) are products of the same gene and express a common mRNA splice form. Brain NAALADase shares the same kinetic profile, pharmacological sensitivities, and immunoreactivity (82% immunoprecipitation by anti-PSMA mAb 7E11-C5) as PSMA from LNCaP prostate tumor cells. Kinetic and pharmacological comparison; Northern blot hybridization; immunoprecipitation with monoclonal antibody; RT-PCR cloning of cerebellar cDNA The Journal of pharmacology and experimental therapeutics High 9694964
1992 NAALADase (FOLH1/GCPII) is a membrane-bound enzyme that cleaves glutamate from the neuropeptide NAAG. Immunocytochemical localization in rat brain showed NAALADase-IR co-localizing with NAAG-IR in neuropil (absent from neuronal cytoplasm), supporting its role in NAAG catabolism in vivo. It was also detected in the brush border of proximal convoluted tubules in the kidney cortex. Immunocytochemistry with specific anti-NAALADase antiserum in rat brain and kidney; co-localization with NAAG-IR The Journal of comparative neurology Medium 1545010
2016 FOLH1/GCPII enzymatic activity is robustly elevated (2.8–41-fold) in affected intestinal mucosa of IBD patients versus uninvolved areas or healthy controls. Genetic knockout of FOLH1 in mice conferred resistance to DSS-induced colitis, and pharmacological inhibition with 2-PMPA (IC50=300 pM) reduced GCPII activity in colonic mucosa by >90% and substantially ameliorated disease in both DSS and IL-10-/- colitis models. Enzymatic activity quantification in 31 surgical specimens; FOLH1 knockout mouse model (DSS colitis); pharmacological inhibition with 2-PMPA in two murine IBD models; macroscopic and microscopic disease assessment JCI insight High 27536732
2018 Sox7 negatively regulates PSMA (FOLH1) expression by directly binding to SOX box sites #2 and #4 within the PSMA enhancer (PSME). The nuclear localization signal (NLS) regions of Sox7, but not its β-catenin interacting motif, are essential for this suppressive activity. Stable expression of canonical Sox7 in LNCaP/C4-2 and 22Rv1 cells suppressed PSMA protein expression. ChIP assay; EMSA; luciferase reporter assay; stable Sox7 overexpression in prostate cancer cell lines; Sox7 domain mutant analysis The Prostate High 30488457
2023 PSMA (FOLH1) expression loss in metastatic castration-resistant prostate cancer is associated with gain of CpG methylation and loss of H3K27 acetylation at the FOLH1 locus. Treatment with HDAC inhibitors reversed this epigenetic repression and restored PSMA expression both in vitro and in vivo. Rapid autopsy cohort PSMA expression profiling; ChIP for H3K27ac; bisulfite methylation analysis; HDAC inhibitor treatment in vitro and in vivo xenograft models JCI insight High 36821396
2016 Cancer cell-conditioned media induces PSMA expression in otherwise PSMA-negative HUVECs both in vitro and in vivo (HUVEC co-implantation mouse model). HUVECs with induced PSMA expression were able to internalize J591 anti-PSMA mAb and PSMA-binding ligand-bearing nanoparticles, demonstrating functional PSMA on induced neovascular endothelium. Conditioned media experiments; in vitro HUVEC PSMA induction assay; in vivo HUVEC co-implantation mouse model; internalization assays with anti-PSMA mAb and nanoparticles Molecular cancer research Medium 27458033
2001 PSMA undergoes internalization via clathrin-coated pits and is recycled like other membrane-bound receptors. Filamin A binding to PSMA reduces the rate of this internalization. Previously described clathrin-coated pit internalization (cited in PMID 12750292); filamin association and internalization rate assay Cancer research Medium 12750292
2001 NAALADase inhibition (by 2-PMPA) reduces extracellular glutamate accumulation and produces a reciprocal rise in extracellular NAAG during cerebral ischemia reperfusion in rats, consistent with FOLH1/GCPII controlling glutamate supply from NAAG hydrolysis in vivo. Suture model of transient middle cerebral artery occlusion in rats; in vivo microdialysis measuring extracellular glutamate and NAAG; pharmacological inhibition with 2-PMPA Annals of the New York Academy of Sciences Medium 10668445
2001 Neuroprotection by NAAG and NAALADase inhibitor 2-PMPA requires the presence of glial cells and group II metabotropic glutamate receptor (mGluR) activation. Selective group II mGlu receptor antagonists reduced protection afforded by both NAAG and 2-PMPA in neuronal/glial co-cultures, while groups I and III mGlu receptor antagonists had no effect. In vitro metabolic inhibition model using neuronal/glial co-cultures vs. neuron-only cultures; pharmacological dissection with selective mGlu receptor agonists and antagonists European journal of pharmacology Medium 11525768
2020 A missense mutation in FOLH1 (rs202676 G allele) is associated with increased FOLH1 mRNA in the dorsolateral prefrontal cortex and decreased NAAG levels (measured by 7-T MRS) in humans. Lower NAAG levels correlated with lower IQ scores and less efficient cortical activity during working memory (fMRI), establishing that FOLH1 genotype influences synaptic NAAG concentration and cognitive function. Human brain mRNA expression analysis; 7-T magnetic resonance spectroscopy (MRS) of NAAG in vivo; cognitive testing; functional MRI during working memory tasks; genetic association with rs202676 The American journal of psychiatry Medium 33256444
2017 Mouse GCPII (Folh1) possesses lower catalytic efficiency but similar substrate specificity and inhibitor sensitivity compared to human GCPII, validating mouse models for inhibitor development. Mouse GCPII is highest expressed in kidney, brain, and salivary glands, but is absent from mouse prostate — a key difference from the human enzyme. Recombinant mouse GCPII preparation; enzymatic kinetic assays; inhibitor panel testing; tissue protein expression profiling FEBS open bio High 28904865
2023 Genetic deletion of GCPII (FOLH1), but not GCPIII, in mice reduced glutamate production, excitotoxicity, and neuronal damage after traumatic brain injury (TBI) and improved cognitive function. Combined GCPII/GCPIII knockout showed no additional benefit over GCPII deletion alone, indicating GCPIII does not compensate for GCPII in TBI. CRISPR/Cas9 knockout of GCPII, GCPIII, and GCPII/III in mice; controlled cortical impact TBI model; hippocampal and cortical injury signaling analysis; cognitive function assessment CNS neuroscience & therapeutics High 37349952
2021 Androgen receptor blockade with enzalutamide increases PSMA protein and mRNA expression in prostate cancer cell lines (22Rv1, C4-2, LNCaP) and in vivo in xenograft tumors, demonstrating that androgen receptor signaling negatively regulates FOLH1/PSMA expression. Flow cytometry; immunohistochemistry; 68Ga-PSMA PET/CT in xenograft-bearing mice; in vitro enzalutamide treatment of cell lines International journal of molecular sciences Medium 34299051
2024 Exosomal PSM-E (a PSMA splice variant) inhibits macrophage M2 polarization by recruiting RACK1 and suppressing FAK and ERK signaling pathways, thereby suppressing prostate cancer invasion and metastasis. The protease-associated domain of PSM-E and the fourth WD repeat of RACK1 are required for their interaction. Co-immunoprecipitation; IHC staining; in vitro and in vivo PCa tumorigenesis models; domain deletion/interaction mapping; Western blotting Biomarker research Medium 39538297

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. Journal of cellular biochemistry 666 14755683
2016 PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 492 26985056
2016 Current use of PSMA-PET in prostate cancer management. Nature reviews. Urology 478 26902337
2015 68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 424 26089548
2014 Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer cell international 167 24645697
2018 A Perspective on the Evolving Story of PSMA Biology, PSMA-Based Imaging, and Endoradiotherapeutic Strategies. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 144 29674422
2001 Cloning, expression, genomic localization, and enzymatic activities of the mouse homolog of prostate-specific membrane antigen/NAALADase/folate hydrolase. Mammalian genome : official journal of the International Mammalian Genome Society 142 11210180
2017 Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 141 28775203
2018 Neuroendocrine differentiation of prostate cancer leads to PSMA suppression. Endocrine-related cancer 138 30400059
2019 PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy. Seminars in nuclear medicine 126 31227053
2021 Advances in PSMA-targeted therapy for prostate cancer. Prostate cancer and prostatic diseases 117 34050265
2020 Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving 177Lu-PSMA-617 Radioligand Therapy. Theranostics 115 32685021
2024 Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer. Nature reviews. Urology 100 38977769
2016 The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease. British journal of pharmacology 96 27526115
2001 A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Genomics 90 11350116
1992 Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase). The Journal of comparative neurology 87 1545010
1998 Molecular characterization of human brain N-acetylated alpha-linked acidic dipeptidase (NAALADase). The Journal of pharmacology and experimental therapeutics 79 9694964
2017 PSMA expression by microvasculature of thyroid tumors - Potential implications for PSMA theranostics. Scientific reports 75 28701709
2003 Prostate-specific membrane antigen association with filamin A modulates its internalization and NAALADase activity. Cancer research 74 12750292
2018 Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clinical & experimental metastasis 69 29426963
2012 GCPII imaging and cancer. Current medicinal chemistry 68 22304713
2023 Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer. JCI insight 67 36821396
2017 Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 66 28986509
2017 Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer. PloS one 65 29077706
2001 Four PSM/SH2-B alternative splice variants and their differential roles in mitogenesis. The Journal of biological chemistry 63 11502739
2020 PSMA expression on neovasculature of solid tumors. Histology and histopathology 61 32282924
2017 PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer. Theranostics 56 28744329
2019 Lutetium-177 prostate-specific membrane antigen (PSMA) theranostics: practical nuances and intricacies. Prostate cancer and prostatic diseases 55 31595044
2012 Glutamate in CNS neurodegeneration and cognition and its regulation by GCPII inhibition. Current medicinal chemistry 52 22304712
2008 Expression and distribution of 'high affinity' glutamate transporters GLT1, GLAST, EAAC1 and of GCPII in the rat peripheral nervous system. Journal of anatomy 51 19014361
2023 PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials. The oncologist 50 36806966
2017 Metal-Based PSMA Radioligands. Molecules (Basel, Switzerland) 50 28338640
2022 PSMA Expression in Solid Tumors beyond the Prostate Gland: Ready for Theranostic Applications? Journal of clinical medicine 49 36362824
2001 PSMA specific antibodies and their diagnostic and therapeutic use. Expert opinion on investigational drugs 49 11227049
2021 Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. International journal of molecular sciences 46 34299051
2017 PSMA Uptake in Mediastinal Sarcoidosis. Clinical nuclear medicine 46 28114227
2016 Still NAAG'ing After All These Years: The Continuing Pursuit of GCPII Inhibitors. Advances in pharmacology (San Diego, Calif.) 46 27288079
2016 A PSMA-targeted theranostic agent for photodynamic therapy. Journal of photochemistry and photobiology. B, Biology 43 28063300
2021 PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga. Hepatology communications 41 34783177
2014 Heterobivalent agents targeting PSMA and integrin-αvβ3. Bioconjugate chemistry 41 24410012
1999 Molecular expression of PSMA mRNA and protein in primary renal tumors. International journal of cancer 41 10074909
2020 Association of Missense Mutation in FOLH1 With Decreased NAAG Levels and Impaired Working Memory Circuitry and Cognition. The American journal of psychiatry 40 33256444
2016 PSM-Mec-A Virulence Determinant that Connects Transcriptional Regulation, Virulence, and Antibiotic Resistance in Staphylococci. Frontiers in microbiology 40 27597849
2015 PSMA expression is highly homogenous in primary prostate cancer. Applied immunohistochemistry & molecular morphology : AIMM 40 26153794
2022 Hetero-bivalent agents targeting FAP and PSMA. European journal of nuclear medicine and molecular imaging 38 35965291
2021 Total tumor volume reduction and low PSMA expression in patients receiving Lu-PSMA therapy. Theranostics 38 34373733
2016 FOLH1/GCPII is elevated in IBD patients, and its inhibition ameliorates murine IBD abnormalities. JCI insight 37 27536732
2020 Prostate-specific membrane antigen (PSMA) expression in adenoid cystic carcinoma of the head and neck. BMC cancer 36 32503460
2016 Small-molecule PSMA ligands. Current state, SAR and perspectives. Journal of drug targeting 36 26887438
2018 Expression of Prostate-Specific Membrane Antigen (PSMA) in Brain Glioma and its Correlation with Tumor Grade. Iranian journal of pathology 35 29731795
2016 Induction of PSMA and Internalization of an Anti-PSMA mAb in the Vascular Compartment. Molecular cancer research : MCR 35 27458033
2019 Renal Cell Carcinoma: the Oncologist Asks, Can PSMA PET/CT Answer? Current urology reports 34 31605269
2022 Upregulation of PSMA Expression by Enzalutamide in Patients with Advanced mCRPC. Cancers 32 35406467
2020 Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors. Journal of medicinal chemistry 32 32852205
2007 Relations of glutamate carboxypeptidase II (GCPII) polymorphisms to folate and homocysteine concentrations and to scores of cognition, anxiety, and depression in a homogeneous Norwegian population: the Hordaland Homocysteine Study. The American journal of clinical nutrition 29 17684227
2017 Comparison of PSMA-HBED and PSMA-I&T as diagnostic agents in prostate carcinoma. European journal of nuclear medicine and molecular imaging 28 28474140
2023 PSMA-targeted therapy for non-prostate cancers. Frontiers in oncology 26 37645427
2022 Radiosynthesis and Preclinical Evaluation of Bispecific PSMA/FAP Heterodimers for Tumor Imaging. Pharmaceuticals (Basel, Switzerland) 26 35337180
2022 Pharmacological Optimization of PSMA-Based Radioligand Therapy. Biomedicines 26 36551776
2021 The VISION Forward: Recognition and Implication of PSMA-/18F-FDG+ mCRPC. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 26 34933889
2019 68Ga-PSMA PET thyroid incidentalomas. Hormones (Athens, Greece) 26 30989578
2001 Neuroprotection afforded by NAAG and NAALADase inhibition requires glial cells and metabotropic glutamate receptor activation. European journal of pharmacology 26 11525768
2022 Diverse PSMA expression in primary prostate cancer: reason for negative [68Ga]Ga-PSMA PET/CT scans? Immunohistochemical validation in 40 surgical specimens. European journal of nuclear medicine and molecular imaging 24 35556160
2021 Ga-68 PSMA PET/CT in recurrent high-grade gliomas: evaluating PSMA expression in vivo. Neuroradiology 24 34648046
1999 Blockade of NAALADase: a novel neuroprotective strategy based on limiting glutamate and elevating NAAG. Annals of the New York Academy of Sciences 24 10668445
2017 [PSMA-targeted radioligand therapy in prostate cancer]. Der Urologe. Ausg. A 23 27885457
2020 Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions. Diagnostic pathology 21 32703222
2019 Synthesis and biological evaluation of PSMA-targeting paclitaxel conjugates. Bioorganic & medicinal chemistry letters 21 31248772
2017 Mouse glutamate carboxypeptidase II (GCPII) has a similar enzyme activity and inhibition profile but a different tissue distribution to human GCPII. FEBS open bio 21 28904865
2023 The current status of prostate cancer treatment and PSMA theranostics. Therapeutic advances in medical oncology 20 37424944
2017 Glutamate carboxypeptidase II (GCPII) inhibitor 2-PMPA reduces rewarding effects of the synthetic cathinone MDPV in rats: a role for N-acetylaspartylglutamate (NAAG). Psychopharmacology 20 28251297
2003 Expression pattern of mouse homolog of prostate-specific membrane antigen (FOLH1) in the transgenic adenocarcinoma of the mouse prostate model. The Prostate 20 12712410
2022 Relative Efficacy of 225Ac-PSMA-617 and 177Lu-PSMA-617 in Prostate Cancer Based on Subcellular Dosimetry. Molecular imaging and radionuclide therapy 19 35114745
2020 Intra-individual dynamic comparison of 18F-PSMA-11 and 68Ga-PSMA-11 in LNCaP xenograft bearing mice. Scientific reports 19 33273603
2019 Looking for Drugs in All the Wrong Places: Use of GCPII Inhibitors Outside the Brain. Neurochemical research 19 31749072
2023 The Potential of PSMA as a Vascular Target in TNBC. Cells 18 36831218
2022 Lutetium-177-PSMA-617: A Vision of the Future. Cancer biology & therapy 18 35220877
2022 [68Ga]Ga-PSMA PET/MRI, histological PSMA expression and preliminary experience with [177Lu]Lu-PSMA therapy in relapsing high-grade glioma. Frontiers in oncology 18 36119502
2017 Local enema treatment to inhibit FOLH1/GCPII as a novel therapy for inflammatory bowel disease. Journal of controlled release : official journal of the Controlled Release Society 18 28159515
2022 Expression of Prostate Specific Membrane Antigen (PSMA) in Breast Cancer. Geburtshilfe und Frauenheilkunde 16 35027860
2003 Conformational and SAR analysis of NAALADase and PSMA inhibitors. Bioorganic & medicinal chemistry 16 13129582
2021 Antihormone treatment differentially regulates PSA secretion, PSMA expression and 68Ga-PSMA uptake in LNCaP cells. Journal of cancer research and clinical oncology 15 33760944
2016 MADD-FOLH1 Polymorphisms and Their Haplotypes with Serum Lipid Levels and the Risk of Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population. Nutrients 15 27070640
2019 Synthesis and biological evaluation of Doxorubicin-containing conjugate targeting PSMA. Bioorganic & medicinal chemistry letters 14 30904185
2013 Association of APOE, GCPII and MMP9 polymorphisms with common diseases and lipid levels in an older adult/elderly cohort. Gene 14 24291031
2008 Essential role of PSM/SH2-B variants in insulin receptor catalytic activation and the resulting cellular responses. Journal of cellular biochemistry 14 17615553
2022 Expression of Prostate-specific Membrane Antigen (PSMA) in Papillary Renal Cell Carcinoma - Overview and Report on a Large Multicenter Cohort. Journal of Cancer 13 35399715
2018 Inhibitor-GCPII Interaction: Selective and Robust System for Targeting Cancer Cells with Structurally Diverse Nanoparticles. Molecular pharmaceutics 13 29389139
2018 Aptamers and apple pies: a mini-review of PSMA aptamers and lessons from Donald S. Coffey. American journal of clinical and experimental urology 13 29666835
2013 GCPII modulates oxidative stress and prostate cancer susceptibility through changes in methylation of RASSF1, BNIP3, GSTP1 and Ec-SOD. Molecular biology reports 13 23979608
2024 CB307: A Dual Targeting Costimulatory Humabody VH Therapeutic for Treating PSMA-Positive Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 12 38593226
2023 Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas. The British journal of radiology 12 36728839
2019 GCPII and its close homolog GCPIII: from a neuropeptidase to a cancer marker and beyond. Frontiers in bioscience (Landmark edition) 12 30844704
2018 Sox7 negatively regulates prostate-specific membrane antigen (PSMA) expression through PSMA-enhancer. The Prostate 12 30488457
2012 GCPII variants, paralogs and orthologs. Current medicinal chemistry 12 22304710
2024 Exosomal PSM-E inhibits macrophage M2 polarization to suppress prostate cancer metastasis through the RACK1 signaling axis. Biomarker research 11 39538297
2023 Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R. Cancers 11 37190273
2023 Deletion of glutamate carboxypeptidase II (GCPII), but not GCPIII, provided long-term benefits in mice with traumatic brain injury. CNS neuroscience & therapeutics 11 37349952
2023 Standardized PSMA-PET Imaging of Advanced Prostate Cancer. Seminars in nuclear medicine 11 37573199
2018 Association of FOLH1, DHFR, and MTHFR gene polymorphisms with susceptibility of Neural Tube Defects: A case control study from Eastern India. Birth defects research 11 30120883

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