SynthesisPharmacological research2023
Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.
Synthesis in Pharmacological research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Cholesterol nose-to-brain delivery as a possible therapeutic strategy in Huntington's disease.Translational neurodegeneration · 2026Article
- From astrocyte cholesterol synthesis to synaptic dysfunction: mechanisms of neuron-glia lipid coupling.Molecular biology reports · 2026Review
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Next-generation neurotherapeutics: nanotechnology, immunotherapy, and gene editing for neurodegenerative diseases.Neurodegenerative disease management · 2025Review
- Impairment of lysosomal quality control in Huntington disease.Cell death & disease · 2025Article
- Astrocyte-neuron combined targeting for CYP46A1 gene therapy in Huntington's disease.Acta neuropathologica communications · 2025Article
- Restoration of CB1 receptor function in hippocampal GABAergic neurons rescues memory deficits in Huntington's disease models.Translational neurodegeneration · 2025Article
- Body mass index-specific metabolic profiles in schizophrenia: implications for cognitive dysfunction and psychopathology.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Absence of hippocampal pathology persists in the Q175DN mouse model of Huntington's disease despite elevated HTT aggregation.Journal of Huntington's disease · 2025Article
- The nonlinear association of ratio of total cholesterol to high density lipoprotein with cognition ability: evidence from a community cohort in China.Frontiers in nutrition · 2025Article
- Role of Liposomes in the Treatment of Neurodegenerative Disorders: A Comprehensive Review.Central nervous system agents in medicinal chemistry · 2025Review
- Brain cholesterol therapy for Huntington's disease - Does it make sense?Clinical and translational medicine · 2024Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
27 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages is sufficient to normalize cognitive defects up to 5 months, as well as to improve other behavioral and neuropathological parameters. A multiple cycle treatment combining both early and late treatments ("2 cycle treatment") lasting 6 months generates therapeutic effects for more than 11 months, without severe adverse reactions. Sustained cholesterol delivery to the brain of zQ175DN mice also reduces mutant Huntingtin aggregates in both the striatum and cortex and completely normalizes synaptic communication in the striatal medium spiny neurons compared to saline-treated HD mice. Furthermore, through a meta-analysis of published and current data, we demonstrated the power of hybrid-g7-NPs-chol and other strategies able to increase brain cholesterol biosynthesis, to reverse cognitive decline and counteract the formation of mutant Huntingtin aggregates. These results demonstrate that cholesterol delivery via brain-permeable NPs is a therapeutic option to sustainably reverse HD-related behavioral decline and neuropathological signs over time, highlighting the therapeutic potential of cholesterol-based strategies in HD patients. DATA AVAILABILITY: This study does not include data deposited in public repositories. Data are available on request to the corresponding authors.
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