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

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Item Type:	Article
Title:	An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration
Creators Name:	Lehmann, S.M., Krueger, C., Park, B., Derkow, K., Rosenberger, K., Baumgart, J., Trimbuch, T., Eom, G., Hinz, M., Kaul, D., Habbel, P., Kaelin, R., Franzoni, E., Rybak, A., Nguyen, D., Veh, R., Ninnemann, O., Peters, O., Nitsch, R., Heppner, F.L., Golenbock, D., Schott, E., Ploegh, H.L., Wulczyn, F.G. and Lehnardt, S.
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.
Keywords:	Alzheimer Disease, Apoptosis, Brain, Confocal Microscopy, Electrophoretic Mobility Shift Assay, HEK293 Cells, Immunohistochemistry, Inbred C57BL Mice, In Situ Hybridization, Knockout Mice, Membrane Glycoproteins, MicroRNAs, Nerve Degeneration, Neurons, Real-Time Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptor 7, Animals, Mice
Source:	Nature Neuroscience
ISSN:	1097-6256
Publisher:	Nature Publishing Group
Volume:	15
Number:	6
Page Range:	827-835
Date:	June 2012
Official Publication:	https://doi.org/10.1038/nn.3113
PubMed:	View item in PubMed

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