Cited by 138Amyotrophic Lateral Sclerosis ResearchAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease

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Chitramuthu, Babykumari P, Bennett, Hugh P J, Bateman, Andrew·2017·Brain

DOI 10.1093/brain/awx198

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Abstract

Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia. Frontotemporal dementia is an early onset form of dementia, distinct from Alzheimer's disease. The GRN-related form of frontotemporal lobar dementia is a proteinopathy characterized by the appearance of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin have recently been reported but are still not well understood. Gene delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits phenotype progression. Here we review what is currently known concerning the molecular function and mechanism of action of progranulin in normal physiological and pathophysiological conditions in both in vitro and in vivo models. The potential therapeutic applications of progranulin in treating neurodegenerative diseases are highlighted.

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Authors: Chitramuthu, B. P., Bennett, H. P. J., & Bateman, A.
Affiliations: McGill University Health Centre (CA)
Corresponding author: Bennett, Hugh P J
ORCID: Chitramuthu, Babykumari P
Bennett, Hugh P J
Bateman, Andrew
Venue: Brain
Publisher: Oxford University Press (OUP)
Published: 2017-08-18
Volume: 140
Issue: 12
Pages: 3081-3104
ISSN: 0006-8950 (ISSN-L)
1460-2156
DOI: 10.1093/brain/awx198
OpenAlex: W2746890128
Cited by: 138
References: 300
Citations by year: 2026: 6 · 2025: 13 · 2024: 9 · 2023: 14 · 2022: 18 · 2021: 24 · 2020: 27 · 2019: 17 · 2018: 10
FWCI: 1.97
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Brain (publishedVersion)
PubMed (publishedVersion)
Funders: McGill University
Weston Brain Institute
McGill University Health Centre
Canadian Cancer Society Research Institute
Topics: Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: progranulin, GRN gene, frontotemporal lobar degeneration, frontotemporal dementia, neurodegenerative diseases, TDP-43, haploinsufficiency, lysosomal function, neurotrophic factors, gene therapy, Alzheimer's disease, Parkinson's disease, proteinopathies
MeSH terms: Progranulins, Granulins, Animals, Humans, Models, Neurological, Mutation, Intercellular Signaling Peptides and Proteins, Mice, Frontotemporal Lobar Degeneration, TDP-43 Proteinopathies, Frontotemporal Dementia, Haploinsufficiency, Molecular Targeted Therapy, In Vitro Techniques

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Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease

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