MicroRNA regulation of Alzheimer's Amyloid precursor protein expression.
Gene dosage effects of Amyloid precursor protein (APP) can cause familial AD. Recent evidence suggest that microRNA (miRNA) pathways, implicated in gene transcriptional control, could be involved in the development of sporadic Alzheimer's disease (AD). We therefore investigated whether miRNAs could participate in the regulation of APP gene expression. We show that miRNAs belonging to the miR-20a family (that is, miR-20a, miR-17-5p and miR-106b) could regulate APP expression in vitro and at the endogenous level in neuronal cell lines. A tight correlation between these miRNAs and APP was found during brain development and in differentiating neurons. We thus identify miRNAs as novel endogenous regulators of APP expression, suggesting that variations in miRNA expression could contribute to changes in APP expression in the brain during development and disease. This possibility is further corroborated by the observation that a statistically significant decrease in miR-106b expression was found in sporadic AD patients.
Hébert
Sébastien S
SS
Center for Human Genetics, KULeuven, Belgium.
Horré
Katrien
K
Nicolaï
Laura
L
Bergmans
Bruno
B
Papadopoulou
Aikaterini S
AS
Delacourte
André
A
De Strooper
Bart
B
D000199:Actins / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D003720:Densitometry; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D058255:Protease Nexins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C545487:APP protein, human; D000199:Actins; D016564:Amyloid beta-Protein Precursor; D035683:MicroRNAs; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface