ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 133 citations in OpenAlex.
- Results from a pilot study on amiodarone administration in monogenic frontotemporal dementia with granulin mutation.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Trial
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- Targeting Granulin Haploinsufficiency in Frontotemporal Dementia: From Genetic Mechanisms to Therapeutics.International journal of molecular sciences · 2025Review
- PGRN Counteracts the Associations of Abnormal Tau Proteins with Neurodegeneration and Cognitive Decline in Non-demented Adults: A Longitudinal Study.Molecular neurobiology · 2025Article
- The role of endolysosomal progranulin and TMEM106B in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Relationships of PGRN with sTREM2 in AD continuum and non-AD pathophysiology and their reciprocal roles in modulating amyloid pathology: two population-based study.Translational psychiatry · 2025Article
- Prosapogenin A induces GSDME-dependent pyroptosis of anaplastic thyroid cancer through vacuolar ATPase activation-mediated lysosomal over-acidification.Cell death & disease · 2024Article
- Benzoxazole-derivatives enhance progranulin expression and reverse the aberrant lysosomal proteome caused by GRN haploinsufficiency.Nature communications · 2024Article
- Progranulin released from microglial lysosomes reduces neuronal ferroptosis after cerebral ischemia in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Microglial Activation, Tau Pathology, and Neurodegeneration Biomarkers Predict Longitudinal Cognitive Decline in Alzheimer's Disease Continuum.Frontiers in aging neuroscience · 2022Article
- Microglia and astrocyte involvement in neurodegeneration and brain cancer.Journal of neuroinflammation · 2021Review
- Microglia regulate brain progranulin levels through the endocytosis/lysosomal pathway.JCI insight · 2021Article
- Pharmacotherapy for Frontotemporal Dementia.CNS drugs · 2021Review
- Tweaking Progranulin Expression: Therapeutic Avenues and Opportunities.Frontiers in molecular neuroscience · 2021Review
- Loss of TMEM106B potentiates lysosomal and FTLD-like pathology in progranulin-deficient mice.EMBO reports · 2020Article
- TheScience advances · 2020Article
- Approaches to develop therapeutics to treat frontotemporal dementia.Neuropharmacology · 2020Review
- Development of disease-modifying drugs for frontotemporal dementia spectrum disorders.Nature reviews. Neurology · 2020Review
- New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous loss-of-function mutations in the progranulin (GRN) gene cause frontotemporal lobar degeneration with ubiquitin and TAR-DNA binding protein 43-positive inclusions by reduced production and secretion of GRN. Consistent with the observation that GRN has neurotrophic properties, pharmacological stimulation of GRN production is a promising approach to rescue GRN haploinsufficiency and prevent disease progression. We therefore searched for compounds capable of selectively increasing GRN levels. Here, we demonstrate that four independent and highly selective inhibitors of vacuolar ATPase (bafilomycin A1, concanamycin A, archazolid B, and apicularen A) significantly elevate intracellular and secreted GRN. Furthermore, clinically used alkalizing drugs, including chloroquine, bepridil, and amiodarone, similarly stimulate GRN production. Elevation of GRN levels occurs via a translational mechanism independent of lysosomal degradation, autophagy, or endocytosis. Importantly, alkalizing reagents rescue GRN deficiency in organotypic cortical slice cultures from a mouse model for GRN deficiency and in primary cells derived from human patients with GRN loss-of-function mutations. Thus, alkalizing reagents, specifically those already used in humans for other applications, and vacuolar ATPase inhibitors may be therapeutically used to prevent GRN-dependent neurodegeneration.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.