IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

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CX3CR1-Targeted PLGA Nanoparticles Reduce Microglia Activation and Pain Behavior in Rats with Spinal Nerve Ligation

International Journal of Molecular Sciences ◽

10.3390/ijms21103469 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3469

Author(s):

Chan Noh ◽

Hyo Jung Shin ◽

Seounghun Lee ◽

Song I Kim ◽

Yoon-Hee Kim ◽

...

Keyword(s):

Neuropathic Pain ◽

Double Emulsion ◽

Plga Nanoparticles ◽

Spinal Nerve ◽

Spinal Nerve Ligation ◽

Proinflammatory Mediators ◽

Bv2 Cells ◽

New Treatment ◽

Interfering Rna

Activation of CX3CR1 in microglia plays an important role in the development of neuropathic pain. Here, we investigated whether neuropathic pain could be attenuated in spinal nerve ligation (SNL)-induced rats by reducing microglial activation through the use of poly(D,L-lactic-co-glycolic acid) (PLGA)-encapsulated CX3CR1 small-interfering RNA (siRNA) nanoparticles. After confirming the efficacy and specificity of CX3CR1 siRNA, as evidenced by its anti-inflammatory effects in lipopolysaccharide-stimulated BV2 cells in vitro, PLGA-encapsulated CX3CR1 siRNA nanoparticles were synthesized by sonication using the conventional double emulsion (W/O/W) method and administered intrathecally into SNL rats. CX3CR1 siRNA-treated rats exhibited significant reductions in the activation of microglia in the spinal dorsal horn and a downregulation of proinflammatory mediators, as well as a significant attenuation of mechanical allodynia. These data indicate that the PLGA-encapsulated CX3CR1 siRNA nanoparticles effectively reduce neuropathic pain in SNL-induced rats by reducing microglial activity and the expression of proinflammatory mediators. Therefore, we believe that PLGA-encapsulated CX3CR1 siRNA nanoparticles represent a valuable new treatment option for neuropathic pain.

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The role of nuclear factor-[kappa ]B in the biology and treatment of multiple myeloma

Seminars in Oncology ◽

10.1053/sonc.2001.29542 ◽

2001 ◽

Vol 28 (6) ◽

pp. 626-633 ◽

Cited By ~ 3

Author(s):

James R. Berenson ◽

Hongjin M. Ma ◽

Robert Vescio

Keyword(s):

Multiple Myeloma ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Nuclear Factor Kappa

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Phosphorylation of the Regulators, a Complex Facet of NF-κB Signaling in Cancer

Biomolecules ◽

10.3390/biom11010015 ◽

2020 ◽

Vol 11 (1) ◽

pp. 15

Author(s):

Aishat Motolani ◽

Matthew Martin ◽

Mengyao Sun ◽

Tao Lu

Keyword(s):

Transcription Factor ◽

Cardiovascular Diseases ◽

Cancer Progression ◽

Nuclear Factor Kappa B ◽

Nuclear Factor ◽

Malignant Diseases ◽

Future Perspectives ◽

Post Translational Modifications ◽

Site Specific

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes.

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