Cells (Basel, Switzerland), 2023-11, Vol.12 (23), p.2735
2023
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- Autor(en) / Beteiligte
- Titel
- Development of a Polymeric Pharmacological Nanocarrier System as a Potential Therapy for Spinocerebellar Ataxia Type 7
- Ist Teil von
- Cells (Basel, Switzerland), 2023-11, Vol.12 (23), p.2735
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2023
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant inherited disease characterized by progressive ataxia and retinal degeneration. SCA7 belongs to a group of neurodegenerative diseases caused by an expanded CAG repeat in the disease-causing gene, resulting in aberrant polyglutamine (polyQ) protein synthesis. PolyQ ataxin-7 is prone to aggregate in intracellular inclusions, perturbing cellular processes leading to neuronal death in specific regions of the central nervous system (CNS). Currently, there is no treatment for SCA7; however, a promising approach successfully applied to other polyQ diseases involves the clearance of polyQ protein aggregates through pharmacological activation of autophagy. Nonetheless, the blood-brain barrier (BBB) poses a challenge for delivering drugs to the CNS, limiting treatment effectiveness. This study aimed to develop a polymeric nanocarrier system to deliver therapeutic agents across the BBB into the CNS. We prepared poly(lactic-co-glycolic acid) nanoparticles (NPs) modified with Poloxamer188 and loaded with rapamycin to enable NPs to activate autophagy. We demonstrated that these rapamycin-loaded NPs were successfully taken up by neuronal and glial cells, demonstrating high biocompatibility without adverse effects. Remarkably, rapamycin-loaded NPs effectively cleared mutant ataxin-7 aggregates in a SCA7 glial cell model, highlighting their potential as a therapeutic approach to fight SCA7 and other polyQ diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2073-4409eISSN: 2073-4409DOI: 10.3390/cells12232735Titel-ID: cdi_doaj_primary_oai_doaj_org_article_48cb39db2af24ddeacde08888960ac7e
- Format
- –
- Schlagworte
- Analysis, Ataxia, Ataxin, Ataxin-7 - genetics, Ataxin-7 - metabolism, Autophagy, Biocompatibility, Biodegradable materials, Blood-brain barrier, Care and treatment, Central nervous system, Diagnosis, Dosage and administration, Drug delivery, Drugs, Electron microscopes, Fourier transforms, Glial cells, Glycolic acid, Health aspects, Hereditary diseases, Humans, Laboratories, Nanoparticles, nanotechnology, Neurodegeneration, Neurodegenerative diseases, Neuroglia - metabolism, Neuronal-glial interactions, Neurons - metabolism, Oxidative stress, Particle size, pharmacological treatment, Polyglutamine diseases, polymeric nanocarrier, polyQ aggregation, Polyvinyl alcohol, Protein biosynthesis, Proteins, Rapamycin, Reagents, Retinal degeneration, Sirolimus, Spectrum analysis, Spinocerebellar ataxia, spinocerebellar ataxia type 7, Spinocerebellar Ataxias - drug therapy, Spinocerebellar Ataxias - genetics, Tetracycline, Tetracyclines, Trinucleotide repeat diseases, Trinucleotide repeats