ArticleEMBO molecular medicine2020
Striatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington's disease mice.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.Pharmacological research · 2023Pooled it
- Cholesterol nose-to-brain delivery as a possible therapeutic strategy in Huntington's disease.Translational neurodegeneration · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Lipid Messengers: Mechanisms and Clinical Applications of Exosomal Lipids in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Leveraging explainable deep learning methodologies to elucidate the biological underpinnings of Huntington's disease using single-cell RNA sequencing data.BMC genomics · 2024Article
- Neuroprotection by ADAM10 inhibition requires TrkB signaling in the Huntington's disease hippocampus.Cellular and molecular life sciences : CMLS · 2024Article
- U-shaped relationship between non-high-density lipoprotein cholesterol and cognitive impairment in Chinese middle-aged and elderly: a cross-sectional study.BMC public health · 2024Article
- Increased genomic instability and reshaping of tissue microenvironment underlie oncogenic properties ofScience advances · 2024Article
- The translational potential of cholesterol-based therapies for neurological disease.Nature reviews. Neurology · 2023Review
- Genome-wide screening in pluripotent cells identifies Mtf1 as a suppressor of mutant huntingtin toxicity.Nature communications · 2023Article
- The factors associated with cognitive function among community-dwelling older adults in Taiwan.BMC geriatrics · 2023Observational
- Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022Review
- Long-Term Increase in Cholesterol Is Associated With Better Cognitive Function: Evidence From a Longitudinal Study.Frontiers in aging neuroscience · 2021Article
- Striatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington's disease mice.EMBO molecular medicine · 2020Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
A variety of pathophysiological mechanisms are implicated in Huntington's disease (HD). Among them, reduced cholesterol biosynthesis has been detected in the HD mouse brain from pre-symptomatic stages, leading to diminished cholesterol synthesis, particularly in the striatum. In addition, systemic injection of cholesterol-loaded brain-permeable nanoparticles ameliorates synaptic and cognitive function in a transgenic mouse model of HD. To identify an appropriate treatment regimen and gain mechanistic insights into the beneficial activity of exogenous cholesterol in the HD brain, we employed osmotic mini-pumps to infuse three escalating doses of cholesterol directly into the striatum of HD mice in a continuous and rate-controlled manner. All tested doses prevented cognitive decline, while amelioration of disease-related motor defects was dose-dependent. In parallel, we found morphological and functional recovery of synaptic transmission involving both excitatory and inhibitory synapses of striatal medium spiny neurons. The treatment also enhanced endogenous cholesterol biosynthesis and clearance of mutant Huntingtin aggregates. These results indicate that cholesterol infusion to the striatum can exert a dose-dependent, disease-modifying effect and may be therapeutically relevant in HD.
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