ArticleHuman molecular genetics2018
Fingolimod phosphate inhibits astrocyte inflammatory activity in mucolipidosis IV.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Focusing on microglial mitochondria-lysosome crosstalk and neuroinflammation underlying depression: from molecular pathways to potential therapeutic interventions.Frontiers in immunology · 2026Review
- Exploring human plasma proteomic variations in mucolipidosis type IV.Molecular therapy. Methods & clinical development · 2025Article
- TRPML-1 Dysfunction and Renal Tubulopathy in Mucolipidosis Type IV.Journal of the American Society of Nephrology : JASN · 2025Article
- A blood-brain barrier-penetrant AAV gene therapy improves neurological function in symptomatic mucolipidosis IV mice.Molecular therapy. Methods & clinical development · 2024Article
- Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV.Frontiers in molecular neuroscience · 2023Article
- Hotair and Malat1 Long Noncoding RNAs Regulate Bdnf Expression and Oligodendrocyte Precursor Cell Differentiation.Molecular neurobiology · 2022Article
- Sodium alginate microencapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis.Acta biomaterialia · 2022Article
- Article
- White matter abnormalities and iron deposition in prenatal mucolipidosis IV- fetal imaging and pathology.Metabolic brain disease · 2021Article
- Progress in elucidating pathophysiology of mucolipidosis IV.Neuroscience letters · 2021Article
- Proteomics analysis of a human brain sample from a mucolipidosis type IV patient reveals pathophysiological pathways.Orphanet journal of rare diseases · 2021Article
- Inherited disorders of lysosomal membrane transporters.Biochimica et biophysica acta. Biomembranes · 2020Review
- Mice defective in interferon signaling help distinguish between primary and secondary pathological pathways in a mouse model of neuronal forms of Gaucher disease.Journal of neuroinflammation · 2020Article
- Extracellular matrix compression temporally regulates microvascular angiogenesis.Science advances · 2020Article
- Early evidence of delayed oligodendrocyte maturation in the mouse model of mucolipidosis type IV.Disease models & mechanisms · 2020Article
- Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System.International journal of molecular sciences · 2020Review
- TRPML1 Promotes Protein Homeostasis in Melanoma Cells by Negatively Regulating MAPK and mTORC1 Signaling.Cell reports · 2019Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
Mucolipidosis IV (MLIV) is an orphan neurodevelopmental disease that causes severe neurologic dysfunction and loss of vision. Currently there is no therapy for MLIV. It is caused by loss of function of the lysosomal channel mucolipin-1, also known as TRPML1. Knockout of the Mcoln1 gene in a mouse model mirrors clinical and neuropathologic signs in humans. Using this model, we previously observed robust activation of microglia and astrocytes in early symptomatic stages of disease. Here we investigate the consequence of mucolipin-1 loss on astrocyte inflammatory activation in vivo and in vitro and apply a pharmacologic approach to restore Mcoln1-/- astrocyte homeostasis using a clinically approved immunomodulator, fingolimod. We found that Mcoln1-/- mice over-express numerous pro-inflammatory cytokines, some of which were also over-expressed in astrocyte cultures. Changes in the cytokine profile in Mcoln1-/- astrocytes are concomitant with changes in phospho-protein signaling, including activation of PI3K/Akt and MAPK pathways. Fingolimod promotes cytokine homeostasis, down-regulates signaling within the PI3K/Akt and MAPK pathways and restores the lysosomal compartment in Mcoln1-/- astrocytes. These data suggest that fingolimod is a promising candidate for preclinical evaluation in our MLIV mouse model, which, in case of success, can be rapidly translated into clinical trial.
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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.