An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration.
Nat Neurosci
; 15(6): 827-35, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22610069
ABSTRACT
Activation of innate immune receptors by host-derived factors exacerbates CNS damage, but the identity of these factors remains elusive. We uncovered an unconventional role for the microRNA let-7, a highly abundant regulator of gene expression in the CNS, in which extracellular let-7 activates the RNA-sensing Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7. Cerebrospinal fluid (CSF) from individuals with Alzheimer's disease contains increased amounts of let-7b, and extracellular introduction of let-7b into the CSF of wild-type mice by intrathecal injection resulted in neurodegeneration. Mice lacking TLR7 were resistant to this neurodegenerative effect, but this susceptibility to let-7 was restored in neurons transfected with TLR7 by intrauterine electroporation of Tlr7(−/−) fetuses. Our results suggest that microRNAs can function as signaling molecules and identify TLR7 as an essential element in a pathway that contributes to the spread of CNS damage.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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MicroRNAs
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Receptor 7 Toll-Like
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Doença de Alzheimer
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Degeneração Neural
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Neurônios
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article