- Microglia-Neuron Co-Culture
- BBB-on-a-Chip
- 3D Brain Organoids
- Astrocyte-Microglia Interaction Systems
- T Cell Infiltration Models
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Neuroinflammation
Neuroinflammation refers to a persistent inflammatory disease process that affects the peripheral or central nervous system due to the pathologic dysregulation of innate immunity, autoimmune mechanisms or infection. Protheragen employs integrative, MyD88-focused drug discovery services aimed at TLR/IL-1R-MyD88 hyperactivation, microglial/astrocyte activation, axonal demyelination, and other neuroinflammatory processes.
Introduction to Neuroinflammation
Neuroinflammation is a chronic, systemic immune reaction of the central nervous system (CNS) waxing and waning inflammation in exogenous and endogenous triggers, including microglia, astrocytes, and immune cell recruitment from the periphery. Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) are some of the neurodegenerative disorders within the common neurodegeneration spectrum and exhibit global prevalence of around 50 million cases. Evidence suggests TLR/MyD88 axis signaling is a key microglial activation potentiating factor for damaging pro-inflammatory cytokine (TNF-α, IL-1β) production along with neuronal destruction.
Pathogenesis of Neuroinflammation
- TLR/MyD88 signal transduction caused by DAMPs or PAMPs activates microglia through NF-кB and MAPK signaling, joining forces to increase TNF-α, IL-6, and IL-1β. There is also exacerbation of the damage to blood-brain barrier (BBB) and astrocytes transforming into more reactive, synaptic toxicity.
- Adaptive Immune Involvement: Invasive autoimmune Th1/Th17 infiltrate along with autoantibodies actively participate in MyD88 mediated inflammation, increasing rate of neuronal demise and demyelination. Astrocyte stimulation by IL-17 and IFN-γ results in the production of neurotoxic constituents.
Fig.1 Tregs protect against myelin injury by alleviating pyroptosis and neuroinflammation in demyelination induced by LPC. (Y. Wang et al., 2023)MyD88-Targeted Therapeutic Development for Neuroinflammation
| Therapeutic Strategy | Mechanism of Action | Representative Approaches | Development Stage |
| MyD88 Homodimerization Inhibitors (e.g., ST2825) | Blocks MyD88 dimerization, suppressing TLR4-MyD88-NF-κB and NLRP3/caspase-1 signaling. | ST2825: Reduces ROS, TNF-α, IL-6, IL-1β, and MCP-1 in LPS-stimulated microglia and mouse brains. | Preclinical |
| MyD88-Specific Small Molecule Inhibitors (e.g., QUIN-A) | Binds directly to MyD88, inhibiting TLR4-MyD88 signaling and downstream pro-inflammatory cytokine release. | QUIN-A: Suppresses BV2 microglial apoptosis, ROS, and TLR4/MyD88 protein expression; reduces neuroinflammation in animal CSF. | Preclinical |
| TLR4 Antagonists | Inhibit TLR4 activation to modulate MyD88-dependent and -independent pathways. | TAK-242-like agents: Suppress NF-κB/NLRP3 and promote phagocytosis via MyD88-independent TRIF pathways. | Preclinical/Phase I (repurposing) |
| MyD88-Independent TLR4 Agonists | Activate TRIF-dependent pathways to enhance glial phagocytosis without pro-inflammatory cytokine release. | TRIF-biased TLR4 agonists: Promote Aβ/α-synuclein clearance in neurodegenerative models. | Experimental |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen develops advanced disease models for Neuroinflammation as well as MyD88-targeted therapeutic discovery. For MyD88 signaling modulator screening and TLR/IL-1R-driven neuroinflammatory pathways, along with neuronal damage and synaptic loss in neurodegenerative diseases, we integrate cutting-edge in vitro and in vivo models on CNS-specific platforms.
Therapeutic Discovery Platform for Neuroinflammation
Protheragen's MyD88 discovery platform for neuroinflammation incorporates pathway-specific modulators with neuro-immune disease models to address disrupted microglia-neuron-astrocyte crosstalk. Through novel inhibitors, degraders, or biologics, the platform achieves preclinical validation of neuroinflammation-driven pathology by targeting MyD88-dependent cytokine networks and synergizing with CNS-penetrant therapies.
Disease Models Development for Neuroinflammation
Protheragen offers full-spectrum preclinical models of neuroinflammation, spanning cell-based models, organoid models, and animal models that recapitulate the complexity of CNS immune dysregulation.
- LPS-Induced Neuroinflammation
- APP/PS1 Transgenic Mice
- Experimental Autoimmune Encephalomyelitis (EAE)
- hTREM2-Humanized Mice
- α-Synuclein AAV Models
Through the treatment options framework for Protheragen, MyD88 related diseases are pursued aggressively. This is done by building comprehensive proposal tools ranging from disease model development, pharmacokinetics and drug safety evaluation, and other focus areas including investigator-initiated trials that aim to expedite the primary assessment stage.
If you are interested in our services, please don't hesitate to contact us.
References
- Saadh, M. J., et al. "Mir-199a-3p Suppresses Neuroinflammation by Directly Targeting Myd88 in a Mouse Model of Bone Cancer Pain." Life Sci 333 (2023): 122139.
- Wang, Y., et al. "Regulatory T Cells Alleviate Myelin Loss and Cognitive Dysfunction by Regulating Neuroinflammation and Microglial Pyroptosis Via Tlr4/Myd88/Nf-Kappab Pathway in Lpc-Induced Demyelination." J Neuroinflammation 20.1 (2023): 41.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.