In vivo ribozyme targeting of betaAPP+ mRNAs.
Mol Cell Biol Res Commun
; 4(4): 239-47, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11409919
ABSTRACT
In Alzheimer's disease (AD) and Down's syndrome (DS) patients, posttranscriptional alterations of sequences encoded by exon 9 and exon 10 of the beta-amyloid precursor protein (betaAPP) mRNA result in mutant proteins (betaAPP+) that colocalize with neurofibrillary tangles and senile plaques. These aberrant messages may contribute to the development of sporadic or late-onset Alzheimer's disease; thus, eliminating them or attenuating their expression could significantly benefit AD patients. In the present work, self-cleaving hammerhead ribozymes targeted to betaAPP exon 9 (Rz9) and betaAPP+ mutant exon 10 (Rz10) were examined for their ability to distinguish between betaAPP and betaAPP+ mRNA. In transiently transfected A-204 cells, quantitative confocal fluorescence microscopy showed that Rz9 preferentially lowered endogenous betaAPP. In contrast, in transient cotransfection experiments with betaAPP+ mRNAs containing a wild-type exon 9 and mutant exon 10 (betaAPP-9/betaAPP-10+1), or a mutant exon 9 and wild-type exon 10 (betaAPP-9+1/betaAPP-10) we found that Rz9 and Rz10 preferentially reduced betaAPP+ -mutant exon 10 mRNA in a concentration and a ribozyme-dependent manner.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
/
RNA Catalítico
/
Precursor de Proteína beta-Amiloide
Limite:
Humans
Idioma:
En
Revista:
Mol Cell Biol Res Commun
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos