Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

Ma, Yanlin; Li, Jianxue; Chiu, Isaac M.; Wang, Yawen; Lü, Jining; Kosaras, Béla; Sidman, Richard L.; Volpe, Joseph J.; Vartanian, Timothy

doi:10.1083/jcb.200606016

Cited by 244 publications

(259 citation statements)

References 20 publications

Supporting

Mentioning

243

Contrasting

Unclassified

Order By: Relevance

“…In Ma's study, they applied 500 μmol/L loxoribine to cultured neurons and did not detect a negative effect on neurite outgrowth [31] . We used 1 mmol/L loxoribine and did find a reduction of dendritic length [11] .…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 96%

“…Thus, they concluded that the negative effect of R848 is mediated via TLR8 but not TLR7 [31] . However, their results are in conflict to many recent studies from various laboratories regarding the expression of TLR7 in neurons [10,11,20,32] , as evidenced by the results of in situ hybridization, quantitative polymerase chain reaction (Q-PCR), and immunostaining using TLR7 antibodies [10,11,20,32] .…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 98%

“…In cultured dorsal root ganglion, cortical, and hippocampal neurons, treatment with poly I:C, a synthetic dsRNA, induces growth-cone collapse and inhibits neurite outgrowth [30] . The effect of poly I:C is mediated via TLR3 because neurons lacking functional TLR3 do [30,61] TLR7 ssRNA CL075, Loxoribine, R848 [11,20,21,32] let-7, miR-21, miR-29a [20,21,32] TLR8 R848 [31] ?…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

“…In addition to TLR3, TLR7 and TLR8 have also been suggested to negatively regulate neurite outgrowth in mouse cortical neurons [11,31] . Ma and colleagues showed that R848, an imidazoquinoline compound, inhibits neurite outgrowth and triggers apoptosis in cortical neurons [31] .…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

“…Ma and colleagues showed that R848, an imidazoquinoline compound, inhibits neurite outgrowth and triggers apoptosis in cortical neurons [31] .…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

See 4 more Smart Citations

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

2014

View full text Add to dashboard Cite

The central nervous system is recognized as an immunoprivileged site because peripheral immune cells do not typically enter it. Microglial cells are thought to be the main immune cells in brain. However, recent reports have indicated that neurons express the key players of innate immunity, including Toll-like receptors (TLRs) and their adaptor proteins (Sarm1, Myd88, and Trif), and may produce cytokines in response to pathogen infection. In the absence of an immune challenge, neuronal TLRs can detect intrinsic danger signals and modulate neuronal morphology and function. In this article, we review the recent fi ndings on the involvement of TLRs and Sarm1 in controlling neuronal morphogenesis and neurodegeneration. Abnormal behaviors in TLRand Sarm1-defi cient mice are also discussed.

show abstract

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 96%

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 98%

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

“…Ma and colleagues showed that R848, an imidazoquinoline compound, inhibits neurite outgrowth and triggers apoptosis in cortical neurons [31] .…”

Section: Tlrs and Neuronal Morphogenesismentioning

confidence: 99%

See 3 more Smart Citations

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

2014

View full text Add to dashboard Cite

show abstract

Neonatal encephalitis and white matter injury: More than just inflammation?

Volpe

2008

Annals of Neurology

Self Cite

View full text Add to dashboard Cite

In this issue of the Annals, Verboon-Maciolek and coworkers show that human parechovirus (HPeV), specifically HPeV3, is an important cause of neonatal viral encephalitis.1 The six serotypes of HPeVs that are included in the genus Parechovirus are small single-stranded (ss) RNA viruses belonging to the family Picornaviridae.2 , 3 These viruses bear many similarities with another and better-known Picornaviridae genus, Enterovirus (EV). Indeed, the genus Parechovirus began with the reclassification of echovirus 21 and 22 as HPeV1 and HPeV2 because of molecular and genetic differences from the remainder of EV. These differences are important because they explain, in part, why the usual polymerase chain reaction (PCR) testing for EV does not detect HPeV. Thus encephalitic infection by HPeV3 has been overlooked in the past, one important point of the current article. (Neonatal encephalitis by other HPeV subtypes is extremely rare and not discussed further.) The encephalitis caused by HPeV3 infection as well as by EV is associated with neonatal seizures and with apparent cerebral white matter injury.1 , 4 The current report has important implications concerning the etiology of neonatal viral encephalitis, the differential diagnosis of neonatal seizures, and the pathology and pathophysiology of the white matter injury.Concerning the etiology of neonatal encephalitis, the findings of Verboon-Maciolek et al.1 indicate that HPeV3 is a major cause. Indeed during the period of their study, neonatal encephalitis due to HPeV3 was three times more common than that due to EV and accounted for 64% of all encephalitic cases admitted to their NICU. Of the major viral infections of the developing nervous system (Table), i.e., rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster, human immunodeficiency virus (HIV), lymphocytic choriomeningitis virus, and EV/HPeV, most are acquired in utero and symptomatic neonatal encephalitis is uncommon (Table).5 HSV and EV/HPeV are associated most consistently with neonatal rather than fetal encephalitis.5 HSV encephalitis exhibits diffuse gray and white matter changes and is discussed elsewhere.5 Neonatal encephalitis caused by EV/HPeV has a distinctive clinical presentation and an apparent predilection for the white matter, as discussed next.Concerning the clinical features of EV/HPeV encephalitis, the usual presentation is fever, rash, irritability and seizures.6 -8 Diarrhea is a common accompaniment, and occurrence in summer and fall, characteristic. Seizures are more common in HPeV3 encephalitis (90%)1 than in EV encephalitis (40%)8 and require more than one anticonvulsant drug for control in most cases. Importantly, the routine CSF examination is normal in 90% of HPeV3 cases and in the majority of EV cases, as well, and therefore on initial clinical evaluation, encephalitis could be easily overlooked. Thus, PCR analysis that includes analysis for HPeV3 as well as EV (and HSV) in CSF and blood is important in the assessment of newborns with

show abstract

Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis

Cited by 244 publications

References 20 publications

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Neonatal encephalitis and white matter injury: More than just inflammation?

Systemic inflammation, oligodendroglial maturation, and the encephalopathy of prematurity

Contact Info

Product

Resources

About