Alzheimer's Disease (AD)
Alzheimer' s Disease (AD) is a chronic or persistent neurodegenerative disease with cognitive, behavioral, and pathological features of gradual memory loss and decline in performance linked to the deposition of Aβ plaques and the presence of tau neurofibrillary tangles. Protheragen provides MyD88-focused drug discovery services to mitigate neuroinflammation and protect neurons, addressing AD pathology including glial activation, neurotoxic mediator release, and synaptic dysfunction.
Introduction to Alzheimer' s Disease
AD has an exponentially ever-increasing prevalence in later stages of life. It has affected millions of people globally. It is a concern in terms of health care, social welfare, and finance. While Aβ and tau pathology are certainly characteristic features of Alzheimer' s, nowadays, neuroinflammation is regarded to be important in the development and advancement of the disease. A number of researchers have emphasized in their publication the TLR/IL-1R/MyD88 signaling pathway as highly important in maintaining glial activation and aberrant cytokine and chemokine like secretion of IL-1β, TNF-α, CXCL10, synaptic disarray, neural destruction and amplifying Aβ and tau pathologies.
Pathogenesis of Alzheimer' s Disease
In Alzheimer' s disease (AD), the interplay between proteinopathy and neuroinflammation drives pathogenesis. Aβ aggregates, tau tangles, and danger-associated molecular patterns (DAMPs) released from stressed or dying neurons activate microglial and astrocytic receptors. This triggers MyDDosome assembly (via Death Domain [DD]-dependent oligomerization of MyD88), which activates MyD88-dependent NF-κB and MAPK signaling in glial cells. MyD88 signaling induces the production of pro-inflammatory cytokines (e.g., IL-1β, TNF-α, IL-6) and chemokines that recruit and activate immune cells, exacerbating neuroinflammation and neuronal damage.
Fig.1 The primary inducers of inflammation in Alzheimer' s Disease. (Twarowski and Herbet, 2023)MyD88-Targeted Therapeutic Development for Alzheimer' s Disease
| Therapeutic Strategy | Mechanism of Action | Key Findings | Development Stage |
| MyD88 Inhibition | Block MyD88-dependent TLR signaling to reduce neuroinflammation. | MyD88 deficiency reduces Aβ load and microglial activation. | Preclinical |
| TLR4 Antagonists (e.g., TAK-242) | Inhibit TLR4-MyD88 signaling to dampen Aβ-induced inflammation. | TLR4 inhibition reduces pro-inflammatory cytokines (IL-1β, TNF-α) in AD models. | Phase I/II (repurposing) |
| CX3CR1 Agonists | Enhance fractalkine signaling to promote MyD88-independent microglial phagocytosis. | MyD88 deficiency increases ApoE-mediated Aβ clearance via CX3CR1 modulation. | Preclinical |
| ApoE Mimetics | Promote Aβ clearance via ApoE pathways, bypassing MyD88-dependent inflammation. | MyD88-KO increases ApoE expression, enhancing Aβ removal. | Preclinical/Phase I |
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' s services include MyD88-targeted therapeutic discovery and advanced disease models development for Alzheimer' s Disease. Our platform integrates neuro-specific in vitro and in vivo models for high-throughput screening of MyD88 signaling modulators, TLR/IL-1R-driven neuroinflammation, and neurodegenerative pathways.
Therapeutic Discovery Platform for Alzheimer' s Disease
Protheragen' s MyD88 discovery platform for Alzheimer' s Disease leverages neuro-immune crosstalk models to rebalance dysregulated innate immune interactions in the brain. The platform accelerates preclinical validation by targeting MyD88-dependent neuroinflammatory networks and mitigating neurotoxicity through novel inhibitors, degraders, or biologics, while synergizing with existing AD strategies.
Disease Models Development for Alzheimer' s Disease
Protheragen provides a complete set of preclinical models for Alzheimer' s Disease, including cell-based models, organoid models, and animal models that recapitulate key aspects of neuroinflammatory and neurodegenerative pathophysiology.
- Primary Human Microglia/Astrocytes
- HMC3 Microglia
- Aβ/Tau-Integrated Brain Organoids
- APOE4/MyD88 Dual-Reporter Organoids
- Tri-Culture Systems
- APP/PS1-MYD88 KO
- TauP301S-MYD88 L265P
- NSG-huMicroglia Mice
- TREM2-R47H Knock-In Mice
- LPS-Induced Neuroinflammation
Protheragen delivers end-to-end solutions for MyD88-related diseases, integrating disease model development, pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed to accelerate preclinical-to-clinical translation.
If you are interested in our services, please don't hesitate to contact us.
References
- Rangasamy, S. B., et al. "Selective Disruption of Tlr2-Myd88 Interaction Inhibits Inflammation and Attenuates Alzheimer's Pathology." J Clin Invest 128.10 (2018): 4297-312.
- Twarowski, B., and M. Herbet. "Inflammatory Processes in Alzheimer's Disease-Pathomechanism, Diagnosis and Treatment: A Review." Int J Mol Sci 24.7 (2023).
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.