ArticleNature communications2016
Prosaposin is a regulator of progranulin levels and oligomerization.
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Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57citing papers in PubMed
5.6field-weighted citation impact, top 4% of its field
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Who cites it
57 citing papers in PubMed, 88 citations in OpenAlex.
- Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial.Nature communications · 2026Trial
- Oligodendrocyte prosaposin restores subarachnoid haemorrhage-induced consciousness impairment.Experimental & molecular medicine · 2026Article
- Accumulation of prosaposin and progranulin around the subfornical organ induces polydipsia in SAP-D-deficient mice.Biochemistry and biophysics reports · 2026Article
- Prosaposin in CNS health and disease, metabolic stress and exercise adaptation.Journal of molecular medicine (Berlin, Germany) · 2026Review
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- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- A novel homozygousThe Journal of international medical research · 2024Article
- Biochemical, Biomarker, and Behavioral Characterization of the GrnMolecular neurobiology · 2024Article
- Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease.Human molecular genetics · 2024Article
- Participation of shrimp pva-miR-166 in hemocyte homeostasis by modulating apoptosis-related geneJournal of virology · 2024Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Biochemical, biomarker, and behavioral characterization of thebioRxiv : the preprint server for biology · 2024Article
- Analytical and clinical validation of a blood progranulin ELISA in frontotemporal dementias.Clinical chemistry and laboratory medicine · 2023Article
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Regulation of extracellular progranulin in medial prefrontal cortex.Neurobiology of disease · 2023Article
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- Integrative Transcriptomic Analyses of Hippocampal-Entorhinal System Subfields Identify Key Regulators in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Surf4, cargo trafficking, lipid metabolism, and therapeutic implications.Journal of molecular cell biology · 2023Review
Corrections and comments
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Authors and funding
40 authors at 14 institutions in 3 countries.
Alexandra M NicholsonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
NiCole A FinchDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Marcio AlmeidaSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Ralph B PerkersonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Marka van BlitterswijkDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Aleksandra WojtasDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Basar CenikDepartment of Neuroscience, Molecular Genetics, and Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Sergio RotondoDepartment of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Venette InskeepDivision of Human Genetics, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Laura AlmasySouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Thomas DyerSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Juan PeraltaSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Goo JunHuman Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Andrew R WoodGenetics of Complex Traits, St Luke's Campus, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
Timothy M FraylingGenetics of Complex Traits, St Luke's Campus, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
Christian FuchsbergerDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Sharon FowlerDepartment of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
Tanya M TeslovichDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Alisa K ManningCenter for Human Genetics Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Satish KumarSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Joanne CurranSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Donna LehmanDepartment of Medicine/Cardiology and Cellular &Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Goncalo AbecasisDepartment of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Ravindranath DuggiralaSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Cyril PottierDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Haaris A ZahirDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Julia E CrookDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Anna KarydasMemory and Aging Center, Department of Neurology, University of California, San Francisco, California 94143, USA.
Laura MiticMemory and Aging Center, Department of Neurology, University of California, San Francisco, California 94143, USA.
Ying SunDivision of Human Genetics, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA.
Dennis W DicksonDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.ORCID 0000-0001-7189-7917
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Joachim HerzDepartment of Molecular Genetics, Neuroscience, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Gang YuDepartment of Molecular Genetics, Neuroscience, Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Bruce L MillerMemory and Aging Center, Department of Neurology, University of California, San Francisco, California 94143, USA.
Shawn FergusonDepartment of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Ronald C PetersenDepartment of Neurology, Mayo Clinic, Rochester, Minnesota 55902, USA.
Neill Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, Florida 32224, USA.
John BlangeroSouth Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, Texas 78520, USA.
Rosa RademakersDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA.
Jacksonville College · USThe University of Texas Rio Grande Valley · USUniversity of California, San Francisco · USUniversity of Michigan · USCincinnati Children's Hospital Medical Center · USSouthwestern Medical Center · USThe University of Texas Health Science Center at San Antonio · USUniversity of Exeter · GBYale University · USMassachusetts General Hospital · USMayo Clinic · USMayo Clinic in Florida · USThe University of Texas Health Science Center at Houston · USThe University of Texas Southwestern Medical Center · US
Funding
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9MMultiethnic Study of Type 2 Diabetes GenesU01DK085526 · NIDDK · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, JABLONSKI, KATHLEEN ANN · 2009 to 2014
$15.7MDiscovery of Functional Variants in Type 2 Diabetes Genes in Mexican AmericansU01DK085524 · NIDDK · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN, DEFRONZO, RALPH A · 2009 to 2019
$5.9MNIDDM SUSCEPTIBILITY GENES IN MEXICAN-AMERICANSR01DK047482 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LEHMAN, DONNA M · 1993 to 2010
$5.4MIdentifying T2D Variants by DNA Sequencing in Multiethnic SamplesU01DK085584 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO, BOEHNKE, MICHAEL L · 2009 to 2013
$4.1MMetabolism of the VLDL receptor and ApoE receptor 2R37HL063762 · NHLBI · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2010 to 2019
$4.0MIdentifying variants causal for Type 2 Diabetes in Major human populationsU01DK085545 · NIDDK · UNIVERSITY OF OXFORD · PI CHAN, JULIANA CN, EBRAHIM, SHAH BRIAN · 2009 to 2013
$2.8MIdentification and Replication of Type 2 Diabetes Genes in Mexican AmericansU01DK085501 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI HANIS, CRAIG L · 2009 to 2013
$2.7MGENETICS OF GALLBLADDER DISEASE IN MEXICAN AMERICANSR01DK053889 · NIDDK · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI DUGGIRALA, RAVINDRANATH · 1998 to 2011
$2.3MMolecular Basis of Synaptic Suppression by ApoER01NS093382 · NINDS · UT SOUTHWESTERN MEDICAL CENTER · PI HERZ, JOACHIM J · 2016 to 2020
$2.0MMolecular genetic studies of progranulin regulators in FTLD and ALSR01NS076471 · NINDS · MAYO CLINIC JACKSONVILLE · PI RADEMAKERS, ROSA · 2013 to 2016
$1.4MNHLBI NIH HHS R37 HL063762NIA NIH HHS P50 AG016574NIA NIH HHS U01 AG006786NIDDK NIH HHS R01 DK047482NIDDK NIH HHS R01 DK053889NIDDK NIH HHS U01 DK085501NIDDK NIH HHS U01 DK085524NIDDK NIH HHS U01 DK085526NIDDK NIH HHS U01 DK085545NIDDK NIH HHS U01 DK085584NINDS NIH HHS R01 NS076471NINDS NIH HHS R01 NS093382
Abstract
Progranulin (GRN) loss-of-function mutations leading to progranulin protein (PGRN) haploinsufficiency are prevalent genetic causes of frontotemporal dementia. Reports also indicated PGRN-mediated neuroprotection in models of Alzheimer's and Parkinson's disease; thus, increasing PGRN levels is a promising therapeutic for multiple disorders. To uncover novel PGRN regulators, we linked whole-genome sequence data from 920 individuals with plasma PGRN levels and identified the prosaposin (PSAP) locus as a new locus significantly associated with plasma PGRN levels. Here we show that both PSAP reduction and overexpression lead to significantly elevated extracellular PGRN levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction. PSAP-induced changes in PGRN levels and oligomerization replicate in human-derived fibroblasts obtained from a GRN mutation carrier, further supporting PSAP as a potential PGRN-related therapeutic target. Future studies should focus on addressing the relevance and cellular mechanism by which PGRN oligomeric species provide neuroprotection.
Indexed as
Alzheimer DiseaseAnimalsFrontotemporal DementiaGene Knockdown TechniquesHaploinsufficiencyHeLa CellsHumansIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutParkinson DiseasePolymorphism, Single NucleotideProgranulinsProtein Interaction MapsSaposinsGRN protein, humanIntercellular Signaling Peptides and ProteinsProgranulinsPSAP protein, humanPsap protein, mouseSaposins
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