ArticleExperimental neurology2016
Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1.
Article in Experimental neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
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- Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.Molecular neurobiology · 2022Review
- Bexarotene Impairs Cognition and Produces Hypothyroidism in a Mouse Model of Down Syndrome and Alzheimer's Disease.Frontiers in pharmacology · 2021Article
- Perspectives on the Role ofJournal of Alzheimer's disease reports · 2021Review
- APOE and Alzheimer's Disease: From Lipid Transport to Physiopathology and Therapeutics.Frontiers in neuroscience · 2021Review
- Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating.Drug delivery and translational research · 2020Article
- Age-Associated DNA Methylation Patterns Are Shared Between the Hippocampus and Peripheral Blood Cells.Frontiers in genetics · 2020Article
- Molecular Insight into the Therapeutic Promise of TargetingOxidative medicine and cellular longevity · 2020Review
- Bexarotene Attenuates Focal Cerebral Ischemia-Reperfusion Injury via the Suppression of JNK/Caspase-3 Signaling Pathway.Neurochemical research · 2019Article
- Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies.Nature reviews. Neurology · 2019Review
- Therapeutic targeting of nuclear receptors, liver X and retinoid X receptors, for Alzheimer's disease.British journal of pharmacology · 2019Review
- APOE and Alzheimer's Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer's Pathogenesis.Molecular neurobiology · 2019Review
- ApoE4: an emerging therapeutic target for Alzheimer's disease.BMC medicine · 2019Review
- Neuroprotective effect of naturally occurring RXR agonists isolated from Sophora tonkinensis Gagnep. on amyloid-β-induced cytotoxicity in PC12 cells.Journal of natural medicines · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (100mg/kg/day) or control diet at the age of 20-24 months for 8 weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-d-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1(-/-) mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neuronal LRP1. However, we also found that bexarotene treatment led to the activation of glial cells, weight loss and hepatomegaly, which are likely due to hepatic failure. Taken together, our results demonstrate that apoE-targeted treatment through the RXR pathway has a potential beneficial effect on synapses during aging; however, the therapeutic application of bexarotene requires extreme caution due to its toxic side effects.
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