@article{Wallach-2021,
  year = {2021},
  publisher = {Sprinter Nature},
  volume = {16},
  number = {80},
  doi = {10.1186/s13024-021-00498-5},
  issn = {1664-302X},
  abstract = "Results: We identified a specific pattern of miRNAs released from apoptotic cortical neurons that activate TLR7 and/or TLR8, depending on sequence and species. Exposure of microglia and macrophages to certain miRNA classes released from apoptotic neurons resulted in the sequence-specific production of distinct cytokines/ chemokines and increased phagocytic activity. Out of those miRNAs miR-100-5p and miR-298-5p, which have consistently been linked to neurodegenerative diseases, entered microglia, located to their endosomes, and directly bound to human TLR8. The miRNA-TLR interaction required novel sequence features, but no specific structure formation of mature miRNA. As a consequence of miR-100-5p- and miR-298-5p-induced TLR activation, cortical neurons underwent cell-autonomous apoptosis. Presence of miR-100-5p and miR-298-5p in cerebrospinal fluid led to neurodegeneration and microglial accumulation in the murine cerebral cortex through TLR7 signaling. 
Conclusion: Our data demonstrate that specific miRNAs are released from apoptotic cortical neurons, serve as endogenous TLR7/8 ligands, and thereby trigger further neuronal apoptosis in the CNS. Our findings underline the recently discovered role of miRNAs as extracellular signaling molecules, particularly in the context of neurodegeneration.
Keywords: Extracellular microRNAs, Endogenous Toll-like receptor ligands, Cortical neurons, Neuronal apoptosis, Microglia, Neurodegeneration, miRNA microarray",
  author = {Thomas Wallach and Zoe Mossmann and Michal Szczepek and Max Wetzel and Rui Machado and Martin Raden and Milad Miladi and Gunnar Kleinau and Christina Kr\"{u}ger and Paul Dembny and Drew Adler and Yuanyuan Zhai and Omar Dzaye and Matthias Futschik and Rolf Backofen and Patrick Scheerer and Seija Lehnardt},
  title = {MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration},
  journal = {Molecular Neurodegeneration},
  user =	 {mmann}
}