Dementia

Dementia is an umbrella term for a decrease in cognitive function such as remembering, thinking, or reasoning, to the extent that hinders a person from performing necessary daily tasks. Protheragen has integrative MyD88-focused drug discovery services that seek to reduce neuroinflammation resulting from TLR/IL-1R-MyD88 hyperactivation, glial activation, synaptopathy, and other processes that lead to various forms of dementia.

Introduction to Dementia

Dementia has thousands of global cases with some common subtypes including Alzheimer's Disease (AD), Vascular Dementia, Frontotemporal Dementia, and Lewy Body Dementia. All these disorders have one thing in common and that is the progressive decline in cognition and share in one form or the other pathological feature which is chronic inflammation of the central nervous system (neuroinflammation). The inflammation is caused by an array of external or internal reasons that are related to every type of dementia through microglia, astrocytes, and immune cells recruited through the periphery.

Pathogenesis of Dementia

The pathogenesis includes signaling through MyD88 dependent TLR/IL-1R within microglia and astrocytes as well as BBB endothelial cells activated by triggers: aggregates of Aβ/tau, vascular injury derived DAMPs and microbial PAMPs. These pathways are triggered to activate NF-κB/MAPK which is accompanied by pro-inflammatory cytokines (release of TNF-α, IL-1β), destruction of blood-brain barrier and toxin concomitantly at the synapse which accelerates the rate of cognitive decline. In some types, adaptive immune responses, i.e., infiltrate T-cells tend to aggravate neuroinflammation due to MyD88 signaling.

Fig.1 Neurotropin alleviates cognitive impairment by inhibiting TLR4/MyD88/NF-κB inflammation signaling pathway in mice with vascular dementia. (Zou et al., 2022)

MyD88-Targeted Therapeutic Development for Dementia

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 dementia as well as MyD88-targeted therapeutic discovery. For MyD88 signaling modulator screening and TLR/IL-1R-driven neuroinflammatory pathways, along with synaptic dysfunction and neuronal damage contributing to cognitive decline, we integrate cutting-edge in vitro and in vivo models on CNS-specific platforms.

Therapeutic Discovery Platform for Dementia

Protheragen's MyD88 discovery platform for dementia incorporates pathway-specific modulators with neuro-immune disease models to address disrupted microglia-neuron-astrocyte crosstalk and other inflammatory processes across different dementia etiologies.

Disease Models Development for Dementia

Protheragen offers full-spectrum preclinical models relevant to dementia and its associated neuroinflammation, spanning cell-based models, organoid models, and animal models, and animal models that recapitulate the complexity of CNS immune dysregulation and neurodegenerative processes.

Cell-based & Organoid models

• Primary Human Microglia/Astrocyte Cultures
• iPSC-Derived Neurons and Glial Cells
• Aβ/Tau-Embedded Organoids
• Vascularized Organoids
• BBB-on-a-Chip

Animal Models Development

• APP/PS1-MYD88 KO Mice
• hTau-MYD88 L252P Mice
• CX3CR1-GFP/MyD88 Reporter Mice
• Aβ-Induced Microstrokes
• TREM2-R47H Knock-In Mice

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

• Schneider, J. A. "Neuropathology of Dementia Disorders." Continuum (Minneap Minn) 28.3 (2022): 834-51.
• Zou, H., et al. "Neurotropin Alleviates Cognitive Impairment by Inhibiting Tlr4/Myd88/Nf-Kappab Inflammation Signaling Pathway in Mice with Vascular Dementia." Neurochem Int 171 (2023): 105625.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.