Cited by 239Lysosomal Storage Disorders ResearchAmyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatments

The DOI matches its Crossref record; 161 of the 161 references it cites were found in a registry or an index.

The lysosomal function of progranulin, a guardian against neurodegeneration

Open access

Paushter, Daniel H., Du, Huan, Feng, Tuancheng, Hu, Fenghua·2018·Acta Neuropathologica

DOI 10.1007/s00401-018-1861-8PMC PMC6117207

Open this paper in CoChat — free account

Abstract

Progranulin (PGRN), encoded by the GRN gene in humans, is a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing and tumorigenesis. The clinical importance of PGRN became especially evident in 2006, when heterozygous mutations in the GRN gene, resulting in haploinsufficiency, were found to be one of the main causes of frontotemporal lobar degeneration (FTLD). FTLD is a clinically heterogenous disease that results in the progressive atrophy of the frontal and temporal lobes of the brain. Despite significant research, the exact function of PGRN and its mechanistic relationship to FTLD remain unclear. However, growing evidence suggests a role for PGRN in the lysosome-most striking being that homozygous GRN mutation leads to neuronal ceroid lipofuscinosis, a lysosomal storage disease. Since this discovery, several links between PGRN and the lysosome have been established, including the existence of two independent lysosomal trafficking pathways, intralysosomal processing of PGRN into discrete functional peptides, and direct and indirect regulation of lysosomal hydrolases. Here, we summarize the cellular functions of PGRN, its roles in the nervous system, and its link to multiple neurodegenerative diseases, with a particular focus dedicated to recent lysosome-related mechanistic developments.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s00401-018-1861-8

Cites

161 of 161 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875
Primary Progressive Aphasia
Weıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058
Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
Cruts, M., Gijselinck, I., van der Zee, J., Engelborghs, S., Wils, H., Pirici, D., Rademakers, R., Vandenberghe, R., Dermaut, B., Martin, J.-J., et al. (2006) · Nature · doi:10.1038/nature05017 · Cited by 1,512
The prevalence of frontotemporal dementia
Ratnavalli, E., Brayne, C., Dawson, K. E., & Hodges, J. R. (2002) · Neurology · doi:10.1212/wnl.58.11.1615 · Cited by 1,182
Sortilin is essential for proNGF-induced neuronal cell death
Nykjaer, A., Lee, R., Teng, K. K., Jansen, P., Madsen, P., Nielsen, M. S., Jacobsen, C., Kliemannel, M., Schwarz, E., Willnow, T. E., et al. (2004) · Nature · doi:10.1038/nature02319 · Cited by 962
The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang, W., Lu, Y., Tian, Q.-Y., Zhang, Y., Guo, F.-J., Liu, G.-Y., Syed, N. M., Lai, Y., Lin, E. A., Kong, L., et al. (2011) · Science · doi:10.1126/science.1199214 · Cited by 761
Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation
Lui, H., Zhang, J., Makinson, S. R., Cahill, M. K., Kelley, K. W., Huang, H.-Y., Shang, Y., Oldham, M. C., Martens, L. H., Gao, F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.001 · Cited by 729

Show all 161 references

Research works printed but not linked: 1

Beutler E, Grabowski G (1995) Guacher disease. The metabolic basis of inherited disease, 7th edn. McGraw-Hill, New York

Sorted by citations

Items 201–239 of 239

Frontotemporal dementia
Sawyer, R. P., Doran, S., & Miller, B. L. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-19176-3.00032-7
Nicorandil treatment improves survival and spatial learning in aged granulin knockout mice
Niedowicz, D. M., Wang, W., Prajapati, P., Zhong, Y., Fister, S. X., Rogers, C. B., Sompol, P. M., Powell, D. K., Patel, I., Norris, C. M., et al. (2024) · Brain Pathology · doi:10.1111/bpa.13312 · Cited by 1
Five Key Criteria for Identifying Optimal Therapeutic Targets in Protein‐Mediated Diseases
Al‐Shuhaib, M. B. S., & Al‐Shuhaib, J. M. B. (2025) · ChemistrySelect · doi:10.1002/slct.202403409
Progranulin-driven lysosomal acidification facilitates exocytosis of PHEV-hijacked lysosomes for viral release
Wang, Z., Chen, Y., He, W., Liu, Y., Jiao, Y., Wang, G., Guan, J., Zhao, K., Zhang, Q., Gao, F., et al. (2025) · mBio · doi:10.1128/mbio.02903-25
Additional file 5 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26658997
Additional file 4 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26658994
Additional file 2 of Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Hasan, S., Fernandopulle, M. S., Humble, S. W., Frankenfield, A. M., Li, H., Prestil, R., Johnson, K. R., Ryan, B. J., Wade‐Martins, R., Ward, M. E., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24580537
Additional file 1 of Progranulin induces immune escape in breast cancer via up-regulating PD-L1 expression on tumor-associated macrophages (TAMs) and promoting CD8+ T cell exclusion
Fang, W., Zhou, T., Shi, H., Yao, M., Zhang, D., Qian, H., Zeng, Q., Wang, Y., Jin, F., Chai, C., et al. (2021) · Figshare · doi:10.6084/m9.figshare.13515589
Additional file 1 of Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia
Kurnellas, M., Mitra, A., Schwabe, T., Paul, R., Arrant, A. E., Roberson, E. D., Ward, M., Yeh, F. L., Long, H., & Rosenthal, A. (2024) · Figshare · doi:10.6084/m9.figshare.26597423
Additional file 2 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.24934656
Additional file 1 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.24934307
Additional file 1 of Fibroblasts from idiopathic Parkinson’s disease exhibit deficiency of lysosomal glucocerebrosidase activity associated with reduced levels of the trafficking receptor LIMP2
Thomas, R., Moloney, E. B., Macbain, Z. K., Hallett, P. J., & Ole Isacson, A. (2021) · Figshare · doi:10.6084/m9.figshare.13612275
Additional file 3 of Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Hasan, S., Fernandopulle, M. S., Humble, S. W., Frankenfield, A. M., Li, H., Prestil, R., Johnson, K. R., Ryan, B. J., Wade‐Martins, R., Ward, M. E., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26641333
Additional file 7 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26659003
Additional file 1 of Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study
Brandes, F., Borrmann, M., Buschmann, D., Meidert, A. S., Reithmair, M., Langkamp, M., Pridzun, L., Kirchner, B., Billaud, J.-N., Amin, N. M., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16564306
Additional file 6 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26659000
Additional file 1 of Dendritic spine head diameter is reduced in the prefrontal cortex of progranulin haploinsufficient mice
Cook, A. K., Greathouse, K. M., Manuel, P. N., Cooper, N. H., Eberhardt, J. M., Freeman, C. D., Weber, A. J., Herskowitz, J. H., & Arrant, A. E. (2024) · Figshare · doi:10.6084/m9.figshare.25980513
Additional file 1 of Differential regulation of progranulin derived granulin peptides
Zhang, T., Du, H., Santos, M. N., Wu, X., Pagan, M. D., Trigiani, L. J., Nishimura, N., Reinheckel, T., & Hu, F. (2022) · Figshare · doi:10.6084/m9.figshare.19126284
Self-citation
Additional file 4 of Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Hasan, S., Fernandopulle, M. S., Humble, S. W., Frankenfield, A. M., Li, H., Prestil, R., Johnson, K. R., Ryan, B. J., Wade‐Martins, R., Ward, M. E., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26641336
Additional file 1 of Multi-modal proteomic characterization of lysosomal function and proteostasis in progranulin-deficient neurons
Hasan, S., Fernandopulle, M. S., Humble, S. W., Frankenfield, A. M., Li, H., Prestil, R., Johnson, K. R., Ryan, B. J., Wade‐Martins, R., Ward, M. E., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24580350
Additional file 3 of Unraveling the intercellular communication disruption and key pathways in Alzheimer’s disease: an integrative study of single-nucleus transcriptomes and genetic association
Liu, A., Fernandes, B. S., Citu, C., & Zhao, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26658991
Progranulin is increased during prodromal pathology in LRRK2 G2019S mice
Moon, S.-H., & Choi, H. J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.153219
Toll-like receptor 9 contributes in microglial activation and lysosomal dysfunction to promote Alzheimer’s diseasePreprint
de Lavergne, M., Mazzola, L., Podsypanina, K., Estrella, C., Verwaerde, P., Evnouchidou, I., Darrasse-Jèze, G., Potier, M., Vyas, S., & Manoury, B. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.16.699962
Résistance des lymphocytes B à la mort cellulaire au cours de la leucémie lymphoïde chronique : implications d'une neurotrophine, le BDNF, du récepteur de la neurotensine, NTSR2, et des "nurse-like cells"
Hugo Talbot, A. (2018) · theses.fr (ABES) · doi:10.70675/eb5fcd35zb3a0z4407zad5czb1de138bd691
Étude de la composante neuroinflammatoire dans les DFT/SLA
Smeyers, J. (2020) · theses.fr (ABES) · doi:10.70675/219cfa6fz5b3az4198z9deczdfaad3cd784c
Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation
Swift, S. K., Huang, G., Cochran, J. N., Albanus, R. D., Minaya, M., Castruita, P. A., Zhang, R., Miller, K. J., Starr, E., Galasso, G., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71352 · Cited by 1
FTDP-17T Mutations Promote Formation of Phosphorylated FTDP-17T TAU Oligomers That Cause Degeneration of Dopaminergic and Hippocampal Neurons via Activating ER Stress and Mitochondrial Pro-apoptotic Cascades
Wang, H.-L., Weng, Y.-H., Chiu, C., Chen, W.-S., Liu, S.-Y., & Yeh, T. (2026) · Neurochemical Research · doi:10.1007/s11064-026-04761-3
Protective TMEM106B-rs3173615 delays age at onset in GRN mutation carriers
Pagano, L., Saraceno, C., Geviti, A., Fostinelli, S., Facconi, A., Laganà, V., Giacomucci, G., Cotelli, M. S., Ingannato, A., Bagnoli, S., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03653-w
GRN rs5848 variant associates with TDP-43 pathology and cancer in opposite directions
Aung, K. Z., Nelson, P. T., Ning, X., Wu, X., Tsuchiya, I., Karanth, S. D., Abner, E. L., Fardo, D. W., & Katsumata, Y. (2026) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlag051
Shared lipidome and proteome signatures of frontotemporal lobar degeneration and Alzheimer’s diseasePreprint
Ambaw, Y. A., Nana, A. L., Li, Z., Singh, S., Monetti, M., Miller, B. L., Spina, S., Grinberg, L. T., Seeley, W. W., Walther, T. C., et al. (2026) · Research Square · doi:10.64898/2026.07.11.737778 · Cited by 1
Biparatopic affibody engineering enables high-affinity sortilin blockade and progranulin elevation
Ek, M., Lindberg, H., Ståhl, S., & Löfblom, J. (2026) · New Biotechnology · doi:10.1016/j.nbt.2026.07.002
Progranulin haploinsufficiency remodels the cerebral microvasculature and neurovascular unitPreprint
Chakraborty, S., Weick, M., Franciosa, S. A., Tabrizi, Z., Swinehart, C., Moore, G. R., Lee, D., Bhatt, N. N., Cano, A., Poorva, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.20.738719
Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer’s disease and advanced Alzheimer’s disease
Thierry, M., Leitner, D., Balcomb, K., Kavanagh, T., Tang, L., Kanshin, E., William, C. M., Oakley, D., Hyman, B. T., Ueberheide, B. M., et al. (2026) · Acta Neuropathologica · doi:10.1007/s00401-026-03064-9
From biology to therapy: advances in progranulin-related neurodegenerative diseases
Hu, S., Qiu, K., Zhen, F., & Zhou, X. (2026) · Molecular Neurodegeneration Advances · doi:10.1186/s44477-026-00042-z
FRONTOTEMPORAL DEMENTIA - COMPREHENSIVE INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND INNOVATIVE TREATMENTS
Wilczkowski, P., Palka, A., Krzysztofek, N., Kopyciński, W., Grzybowska, M., Boszczyk, K., Krawczyk, N., Kamela, M., Baran, A., & Krawczyk, O. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.6339
AZP2006 in Parkinson’s disease models: A promising new neuroprotective treatment involving lysosomal homeostasis and the Progranulin/Prosaposin complex
Callizot, N., Culley, G. R., Flower, G., Rouvière, L., Conto, V. D., Wojcinski, A., Botto, C., Estrella, C., Henriques, A., & Verwaerde, P. (2026) · PLoS ONE · doi:10.1371/journal.pone.0359269
Lysosomal multi-omics reveals altered sphingolipid catabolism associated with lysosomal dysfunction in the aging brain
Sarkar, C., Chen, Y., Nguyen, D. P., Weldemariam, M. M., Morel, Y., Mehrabani-Tabari, A. A., Gorny, N., Pettyjohn-Robin, O., Hegdekar, N., Thapa, S., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118065 · Cited by 2
An Optimized Stem Cell Secretome Proteomics Platform: Application to Progranulin-Deficient iPSCs
Ni, J., Tracey, H. S., & Hao, L. (2026) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6c00588
Progranulin haploinsufficiency disrupts cathepsin D function, resulting in lysosomal abnormalities and elevated TDP-43 levels in the mouse brain
Fazal, R., Tharkeshwar, A. K., Beel, S., Storm, A., Schevenels, B., Tomé, S. O., Thal, D. R., Bosch, L. V. D., Beckers, J., & Damme, P. V. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1970154

Authors: Paushter, D. H., Du, H., Feng, T., & Hu, F.
Affiliations: Cornell University (US)
Corresponding author: Hu, Fenghua
ORCID: Du, Huan
Feng, Tuancheng
Hu, Fenghua
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2018-05-09
Volume: 136
Issue: 1
Pages: 1-17
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-018-1861-8
PMC: PMC6117207
OpenAlex: W2802961407
Cited by: 230
References: 161
Citations by year: 2026: 21 · 2025: 31 · 2024: 33 · 2023: 32 · 2022: 26 · 2021: 45 · 2020: 19 · 2019: 18 · 2018: 3
FWCI: 2.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS088448, R01NS095954)
Topics: Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: progranulin, lysosomes, lysosomal trafficking, frontotemporal lobar degeneration, haploinsufficiency, neuronal ceroid lipofuscinosis, lysosomal storage disease, lysosomal enzymes, neurodegeneration, neurodegenerative diseases
MeSH terms: Progranulins, Animals, Humans, Lysosomes, Models, Biological, Mutation, Neurodegenerative Diseases, Protein Transport

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The lysosomal function of progranulin, a guardian against neurodegeneration

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks