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SARM1, Not MyD88, Mediates TLR7/TLR9-Induced Apoptosis in Neurons
Abstract
Neuronal apoptosis is a key aspect of many different neurologic diseases, but the mechanisms remain unresolved. Recent studies have suggested a mechanism of innate immune-induced neuronal apoptosis through the stimulation of endosomal TLRs in neurons. TLRs are stimulated both by pathogen-associated molecular patterns as well as by damage-associated molecular patterns, including microRNAs released by damaged neurons. In the present study, we identified the mechanism responsible for TLR7/TLR9-mediated neuronal apoptosis. TLR-induced apoptosis required endosomal localization of TLRs but was independent of MyD88 signaling. Instead, apoptosis required the TLR adaptor molecule SARM1, which localized to the mitochondria following TLR activation and was associated with mitochondrial accumulation in neurites. Deficiency in SARM1 inhibited both mitochondrial accumulation in neurites and TLR-induced apoptosis. These studies identify a non–MyD88 pathway of TLR7/ TLR9 signaling in neurons and provide a mechanism for how innate immune responses in the CNS directly induce neuronal damage.
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“neuronal apoptosis induced by ssRNA derived from human endogenous retrovirus K, or the TLR7/8 ligand imiquimod requires SARM1, but not MyD88 [7, 83].”
From Neurodegenerative disease-associated microRNAs acting as signaling molecules modulate CNS neuron structure and viability (2025) · cites this paper as [83]
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Metadata
- Authors
- Mukherjee, P., Winkler, C. W., Taylor, K. G., Woods, T. A., Nair, V., Khan, B. A., & Peterson, K. E.
- Affiliations
- Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT 59840
- Research Technologies Branch, Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Hamilton, MT 59840
- ORCID
- Khan, Burhan A
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-11
- Volume
- 195
- Issue
- 10
- Pages
- 4913-4921
- ISSN
- 0022-1767
- 1550-6606
- PMC
- PMC4769638
- Cited by
- 64
- References
- 37
- Language
- en
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