Novel small-molecule inhibitors like ST2825 appear effective at inhibiting MyD88-dependent pathways, dampening NLRP3/caspase-1 activation and NF-κB neurotoxic effects in relevant models of PD. Preclinical evidence suggests that they reduce LPS- or α-synuclein-induced inflammation and sustain neuronal survival. Efforts are currently directed toward the modification of MyD88 inhibitors to enhance penetration of the blood-brain barrier and selectivity, aiming to take them into clinical studies for PD.
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Parkinson's Disease (PD)
Parkinson's disease is a progressive disorder of the nervous system where there is a loss of dopaminergic neurons, aggregates of alpha-synuclein, and long term inflammation within the brain. Protheragen provides services for the development of therapies using a MyD88 pathway approach which aims to aid clients in modifying their therapy plans by expediting early staging relayed to preclinical steps of the therapeutic pathways.
Introduction to Parkinson's Disease
Parkinson's disease is the second most common neurodegenerative disease in the world, often manifesting with diverse clinical signs and differing rates of disease progression. Its causes are diverse, with complex genetic factors and environmental triggers that result in protein misfolding alongside neuroinflammation. The presence of neuroinflammation due to the action of microglial cells and astrocytes is also a prominent feature of PD, whether it is of sporadic or genetic origin.
Pathogenesis of Parkinson's Disease
In the case of PD, the pathogenesis involves overly relevant neuroinflammation processes relevant within the system and is compared to the system's pathological signaling concerning the dopaminergic neurons degradation. The more advanced and devolving regions of the brain are characterized by the presence of aggregates of alpha synuclein which are misfolded along with DAMPs from stressed of dying neuron which activate PRR receptors on microglia and astrocytes. The Myddosome complex is also activated through MyD88 dependent calcineurin and NF-κB signaling pathways.
Fig.1 Molecular mechanisms contributing to Parkinson's disease. (Morris et al., 2024)MyD88-Targeted Therapeutic Development for Parkinson's Disease
Our Services
Protheragen offers MyD88 targeted therapeutic discovery and advanced disease models development services geared towards Parkinson's Disease. Our models enable preclinical intervention development for aberrantly elevated MyD88 signaling to mitigate inflammation and protect the dopaminergic neurons in PD.
Therapeutic Discovery Platform for Parkinson's Disease
Protheragen has designed a comprehensive MyD88-targeted PD therapeutic discovery platform that focuses on the modulation of neuroinflammatory signaling triggered by elements such as alpha-synuclein and DAMPs. The platform utilizes preclinical pathway-driven disease models intended to interrupt the MyD88-dependent neuroinflammatory circuitry.
Disease Models Development for Parkinson's Disease
Protheragen offers extensive in vitro & in vivo models for Parkinson's Disease, including cell-based models, organoid models, and animal models, enabling the comprehensive evaluation of MyD88-targeted therapeutic strategies. These models recapitulate key aspects of PD pathogenesis, particularly those involving alpha-synuclein pathology and neuroinflammation, providing critical insights into therapeutic efficacy.
- Primary Neuronal Culture
- Immortalized Cell Line
- Brain Organoid Models
- 3D Neurosphere Models
- MPTP-Induced Mouse Models
- SNCA Transgenic Mouse Model
- Parkin Double Knockout Mouse Model
- α-Synuclein Overexpression Model
Protheragen advances MyD88-targeted drug discovery for Parkinson's Disease through end-to-end solutions. We provide comprehensive proposal tools encompassing disease model development, pharmacokinetics and drug safety evaluation, alongside support for investigator-initiated trials.
If you are interested in our services, please don't hesitate to contact us.
References
- Filimontseva, A., et al. "Neuromelanin and Selective Neuronal Vulnerability to Parkinson's Disease." Trends Neurosci (2025).
- Morris, H. R., et al. "The Pathogenesis of Parkinson's Disease." Lancet 403.10423 (2024): 293-304.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.