ArticleMolecular neurodegeneration2018
Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice.
Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 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
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Hippocampal neuronal progranulin mediates estrogen‑deficiency‑induced affective vulnerability and lysosomal-autophagic dysfunction.Molecular psychiatry · 2026Article
- Progranulin: Dose-dependent neurotoxicity.Neural regeneration research · 2026Article
- Progranulin Is a Useful Biomarker to Predict Mortality in ICU Patients with Low Burden of Organ Dysfunction.Biomedicines · 2026Article
- Molecular mechanisms of autophagy-lysosomal pathway dysfunction in neurodegenerative diseases and therapeutic strategies for lysosomal repair: a review.Frontiers in neuroscience · 2026Review
- Article
- Ablation of progranulin augments microglial activation and accelerates prion progression.Acta neuropathologica communications · 2025Article
- Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells.Translational neurodegeneration · 2025Review
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
- Identifying and Diagnosing TDP-43 Neurodegenerative Diseases in Psychiatry.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2024Review
- Increased circulating progranulin is not sufficient to induce cardiac dysfunction or supraventricular arrhythmia.Scientific reports · 2023Article
- Progranulin and GPNMB: interactions in endo-lysosome function and inflammation in neurodegenerative disease.Journal of neuroinflammation · 2023Review
- Targeting Progranulin as an Immuno-Neurology Therapeutic Approach.International journal of molecular sciences · 2023Review
- Latozinemab, a novel progranulin-elevating therapy for frontotemporal dementia.Journal of translational medicine · 2023Article
- Review
- Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors.Journal of neuroinflammation · 2022Article
- The Advance on Frontotemporal Dementia (FTD)'s Neuropathology and Molecular Genetics.Mediators of inflammation · 2022Review
- C9orf72 ALS-FTD: recent evidence for dysregulation of the autophagy-lysosome pathway at multiple levels.Autophagy · 2021Review
- Chemical and genetic rescue of in vivo progranulin-deficient lysosomal and autophagic defects.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTAR DNA binding protein 43 (TDP-43) is the main disease protein in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of patients with frontotemporal dementia (FTD). TDP-43 pathology is not restricted to patients with missense mutations in TARDBP, the gene encoding TDP-43, but also occurs in ALS/FTD patients without known genetic cause or in patients with various other ALS/FTD gene mutations. Mutations in progranulin (GRN), which result in a reduction of ~ 50% of progranulin protein (PGRN) levels, cause FTD with TDP-43 pathology. How loss of PGRN leads to TDP-43 pathology and whether or not PGRN expression protects against TDP-43-induced neurodegeneration is not yet clear.
methodsWe studied the effect of PGRN on the neurodegenerative phenotype in TDP-43(A315T) mice.
resultsPGRN reduced the levels of insoluble TDP-43 and histology of the spinal cord revealed a protective effect of PGRN on the loss of large axon fibers in the lateral horn, the most severely affected fiber pool in this mouse model. Overexpression of PGRN significantly slowed down disease progression, extending the median survival by approximately 130 days. A transcriptome analysis did not point towards a single pathway affected by PGRN, but rather towards a pleiotropic effect on different pathways.
conclusionOur findings reveal an important role of PGRN in attenuating mutant TDP-43-induced neurodegeneration.
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