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Therapeutic correction of ApoER2 splicing in Alzheimer's disease mice using antisense oligonucleotides.
Hinrich, Anthony J; Jodelka, Francine M; Chang, Jennifer L; Brutman, Daniella; Bruno, Angela M; Briggs, Clark A; James, Bryan D; Stutzmann, Grace E; Bennett, David A; Miller, Steven A; Rigo, Frank; Marr, Robert A; Hastings, Michelle L.
Afiliación
  • Hinrich AJ; Department of Cell Biology and Anatomy, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Jodelka FM; Department of Cell Biology and Anatomy, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Chang JL; Department of Cell Biology and Anatomy, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Brutman D; Department of Biology, Lake Forest College, Lake Forest, IL, USA.
  • Bruno AM; Department of Neuroscience, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Briggs CA; Department of Neuroscience, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • James BD; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
  • Stutzmann GE; Department of Neuroscience, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
  • Miller SA; Department of Psychology, College of Health Professions Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Rigo F; Ionis Pharmaceuticals, Carlsbad, CA, USA.
  • Marr RA; Department of Neuroscience, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
  • Hastings ML; Department of Cell Biology and Anatomy, Chicago Medical School Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA michelle.hastings@rosalindfranklin.edu.
EMBO Mol Med ; 8(4): 328-45, 2016 04 01.
Article en En | MEDLINE | ID: mdl-26902204
Apolipoprotein E receptor 2 (ApoER2) is an apolipoprotein E receptor involved in long-term potentiation, learning, and memory. Given its role in cognition and its association with the Alzheimer's disease (AD) risk gene, apoE, ApoER2 has been proposed to be involved in AD, though a role for the receptor in the disease is not clear. ApoER2 signaling requires amino acids encoded by alternatively spliced exon 19. Here, we report that the balance of ApoER2 exon 19 splicing is deregulated in postmortem brain tissue from AD patients and in a transgenic mouse model of AD To test the role of deregulated ApoER2 splicing in AD, we designed an antisense oligonucleotide (ASO) that increases exon 19 splicing. Treatment of AD mice with a single dose of ASO corrected ApoER2 splicing for up to 6 months and improved synaptic function and learning and memory. These results reveal an association between ApoER2 isoform expression and AD, and provide preclinical evidence for the utility of ASOs as a therapeutic approach to mitigate Alzheimer's disease symptoms by improving ApoER2 exon 19 splicing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme del ARN / Oligonucleótidos Antisentido / Proteínas Relacionadas con Receptor de LDL / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Empalme del ARN / Oligonucleótidos Antisentido / Proteínas Relacionadas con Receptor de LDL / Enfermedad de Alzheimer Límite: Animals / Humans Idioma: En Revista: EMBO Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido