ArticleBrain research2009
Allopregnanolone treatment delays cholesterol accumulation and reduces autophagic/lysosomal dysfunction and inflammation in Npc1-/- mouse brain.
Article in Brain research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 76 citations in OpenAlex.
- Mito-TEMPO improves survival rates inScience advances · 2026Article
- Pregnanolone Glutamate: A Dual-Fate Delivery System for Neuroactive Steroids in Perinatal Focal Cerebral Ischemia.International journal of molecular sciences · 2026Article
- Microglia alter sex-specific cerebellar myelination following placental hormone loss.Nature communications · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Age and sex effects of a validated LC-MS/MS method for the simultaneous quantification of testosterone, allopregnanolone, and its isomers in human serum.Scientific reports · 2024Article
- Neurosteroids and their potential as a safer class of general anesthetics.Journal of anesthesia · 2024Review
- Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann-Pick Type C1.International journal of molecular sciences · 2023Article
- Implications of Hypothalamic Neural Stem Cells on Aging and Obesity-Associated Cardiovascular Diseases.Cells · 2023Review
- MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism.International journal of molecular sciences · 2023Review
- Allopregnanolone pleiotropic action in neurons and astrocytes: calcium signaling as a unifying mechanism.Frontiers in endocrinology · 2023Article
- Organ Weights inInternational journal of molecular sciences · 2022Article
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- The Enantiomer of Allopregnanolone Prevents Pressure-Mediated Retinal Degeneration Via Autophagy.Frontiers in pharmacology · 2022Article
- Inflammatory pathophysiological mechanisms implicated in postpartum depression.Frontiers in pharmacology · 2022Review
- The neurosteroid allopregnanolone protects retinal neurons by effects on autophagy and GABRs/GABAAutophagy · 2021Article
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond.Neurobiology of stress · 2019Article
- Reduced Neurosteroid Exposure Following Preterm Birth and Its' Contribution to Neurological Impairment: A Novel Avenue for Preventative Therapies.Frontiers in physiology · 2019Review
- Neurosteroids and oxysterols as potential therapeutic agents for glaucoma and Alzheimer's disease.Neuropsychiatry · 2018Article
- Methyl-β-cyclodextrin restores impaired autophagy flux in Niemann-Pick C1-deficient cells through activation of AMPK.Autophagy · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Niemann-Pick Type C (NPC) disease is a devastating developmental disorder with progressive and fatal neurodegeneration. Previous work has shown that a single injection of the neurosteroid allopregnanolone at postnatal day 7 significantly prolonged lifespan of Npc1-/- mice. However, the cellular/molecular basis for this beneficial effect remains undefined. Here, we further characterized the effect of allopregnanolone treatment on cholesterol accumulation, a pathological hallmark of NPC, as well as on autophagic/lysosomal dysfunction, myelination and inflammation in Npc1-/- mouse brains. At 1 month postnatal, accumulation of filipin-labeled unesterified cholesterol was clearly evident not only in neurons but also in microglia in untreated mutant mice, but was mostly absent in allopregnanolone-treated animals. Brain levels of the lysosomal enzymes cathepsins B and D were significantly higher in Npc1-/- than in wild-type mice. Levels of LC3-II, an autophagy marker, were also increased in mutant mouse brain as compared to wild-type mouse brain. Both changes were significantly reduced by allopregnanolone treatment. Injection of the neurosteroid also significantly reduced astrocyte proliferation and microglial activation. Furthermore, allopregnanolone treatment significantly enhanced myelination in mutant mice. Taken together, our results clearly show that allopregnanolone treatment not only reduces cholesterol accumulation and improves autophagic/lysosomal function but also enhances myelination and reduces inflammation. These results provide further support for the potential usefulness of allopregnanolone for treating NPC disease.
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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.