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Nat Neurosci. 2012 Jun;15(6):827-35. doi: 10.1038/nn.3113.

An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration.

Author information

1
Department of Neurology, Charité-Universitaetsmedizin Berlin, Berlin, Germany.

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.

PMID:
22610069
DOI:
10.1038/nn.3113
[Indexed for MEDLINE]

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