| Autor: |
Borbolla-Jiménez FV; Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación-Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico.; Programa de Ciencias Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico., Del Prado-Audelo ML; Departamento de Bioingeniería, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey Campus Ciudad de México, Ciudad de México 14380, Mexico., Cisneros B; Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Ciudad de México 07360, Mexico., Caballero-Florán IH; Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.; Departamento de Farmacia, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Ciudad de México 07360, Mexico., Leyva-Gómez G; Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico., Magaña JJ; Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación-Luis Guillermo Ibarra Ibarra, Ciudad de México 14389, Mexico.; Departamento de Bioingeniería, Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey Campus Ciudad de México, Ciudad de México 14380, Mexico. |
| Abstrakt: |
Seven of the most frequent spinocerebellar ataxias (SCAs) are caused by a pathological expansion of a cytosine, adenine and guanine (CAG) trinucleotide repeat located in exonic regions of unrelated genes, which in turn leads to the synthesis of polyglutamine (polyQ) proteins. PolyQ proteins are prone to aggregate and form intracellular inclusions, which alter diverse cellular pathways, including transcriptional regulation, protein clearance, calcium homeostasis and apoptosis, ultimately leading to neurodegeneration. At present, treatment for SCAs is limited to symptomatic intervention, and there is no therapeutic approach to prevent or reverse disease progression. This review provides a compilation of the experimental advances obtained in cell-based and animal models toward the development of gene therapy strategies against polyQ SCAs, providing a discussion of their potential application in clinical trials. In the second part, we describe the promising potential of nanotechnology developments to treat polyQ SCA diseases. We describe, in detail, how the design of nanoparticle (NP) systems with different physicochemical and functionalization characteristics has been approached, in order to determine their ability to evade the immune system response and to enhance brain delivery of molecular tools. In the final part of this review, the imminent application of NP-based strategies in clinical trials for the treatment of polyQ SCA diseases is discussed. |
