ArticleNeurobiology of disease2016
CNS uptake of bortezomib is enhanced by P-glycoprotein inhibition: implications for spinal muscular atrophy.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Harnessing Repurposed Drugs to Enhance Temozolomide Efficacy in Glioblastoma.Cancer reports (Hoboken, N.J.) · 2026Review
- Repurposing FDA-approved drugs as inhibitors of therapy-induced invadopodia activity in glioblastoma cells.Molecular and cellular biochemistry · 2023Article
- Quantitative Bioactivity Signatures of Dietary Supplements and Natural Products.ACS pharmacology & translational science · 2023Article
- Bortezomib Pharmacogenetic Biomarkers for the Treatment of Multiple Myeloma: Review and Future Perspectives.Journal of personalized medicine · 2023Review
- A combinatorial approach increases SMN level in SMA model mice.Human molecular genetics · 2022Article
- Review
- The consequence of endothelial remodelling on the blood spinal cord barrier and nociception.Current research in physiology · 2022Review
- The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations.International journal of molecular sciences · 2021Article
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- Transporter-Mediated Delivery of Small Molecule Drugs to the Brain: A Critical Mechanism That Can Advance Therapeutic Development for Ischemic Stroke.Pharmaceutics · 2020Review
- Early Bortezomib Therapy for Refractory Anti-NMDA Receptor Encephalitis.Frontiers in neurology · 2020Article
- Botryllamide G is an ABCG2 inhibitor that improves lapatinib delivery in mouse brain.Cancer biology & therapy · 2020Article
- Bortezomib at therapeutic doses poorly passes the blood-brain barrier and does not impair cognition.Brain communications · 2020Article
- Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment.Frontiers in pharmacology · 2020Review
- Cell-type-specific sensitivity of bortezomib in the methotrexate-resistant primary central nervous system lymphoma cells.International journal of clinical oncology · 2019Article
- Calpain Inhibition Increases SMN Protein in Spinal Cord Motoneurons and Ameliorates the Spinal Muscular Atrophy Phenotype in Mice.Molecular neurobiology · 2019Article
- Synergistic Effects of Bortezomib-OV Therapy and Anti-Invasive Strategies in Glioblastoma: A Mathematical Model.Cancers · 2019Article
- Intraperitoneal delivery of a novel drug-like compound improves disease severity in severe and intermediate mouse models of Spinal Muscular Atrophy.Scientific reports · 2019Article
- Molecular Factors Involved in Spinal Muscular Atrophy Pathways as Possible Disease-modifying Candidates.Current genomics · 2018Review
- Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System.ACS applied materials & interfaces · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The development of therapeutics for neurological disorders is constrained by limited access to the central nervous system (CNS). ATP-binding cassette (ABC) transporters, particularly P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are expressed on the luminal surface of capillaries in the CNS and transport drugs out of the endothelium back into the blood against the concentration gradient. Survival motor neuron (SMN) protein, which is deficient in spinal muscular atrophy (SMA), is a target of the ubiquitin proteasome system. Inhibiting the proteasome in a rodent model of SMA with bortezomib increases SMN protein levels in peripheral tissues but not the CNS, because bortezomib has poor CNS penetrance. We sought to determine if we could inhibit SMN degradation in the CNS of SMA mice with a combination of bortezomib and the ABC transporter inhibitor tariquidar. In cultured cells we show that bortezomib is a substrate of P-gp. Mass spectrometry analysis demonstrated that intraperitoneal co-administration of tariquidar increased the CNS penetrance of bortezomib, and reduced proteasome activity in the brain and spinal cord. This correlated with increased SMN protein levels and improved survival and motor function of SMA mice. These findings show that CNS penetrance of treatment for this neurological disorder can be improved by inhibiting drug efflux at the blood-brain barrier.
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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.