Neurodegenerative Diseases
Neurodegenerative diseases are a range of conditions that result in the gradual loss of a neuron's structure or function, eventually resulting in cell death in the central nervous system. This cell death scenario is seen in Alzheimer's disease, Parkinson's disease, and several forms of dementia. Protheragen is actively pioneering innovative compounds and therapeutic strategies that target the MyD88 pathway, aiming to address critical unmet needs in the research and preclinical development of solutions for neurodegenerative diseases.
Overview of Neurodegenerative Diseases
Neurodegenerative diseases comprise a broad collection of chronic diseases, with the defining feature of the selective and gradual decay of functioning neurons, resulting in neuronal cell death and a progressive decline in the function of the cerebrum. The pathogenesis of these diseases is usually associated with protein aggregation, oxidative stress, and a chronic inflammatory state, termed neuroinflammation. Given the complex and irreversible nature of neuronal loss, there is a pressing need for new treatment options that are capable of stalling or slowing disease advancement.
MyD88 in Neurodegenerative Pathogenesis
Inflammation and its response to injury, in concert with genetics and proteins, are crucial to the development of neurodegenerative disorders. In this regard, the Myeloid Differentiation Primary Response 88 (MyD88) represents a critical component of such a disease in terms of having a role in the potent inflammation response and serving as an adaptor protein that is vital for the relay of signals beneath the major part of the interleukin 1 receptor and Toll-Like Receptors (TLR).
Fig.1 Expression of ACOD1 in infection and immunity. (Wu et al., 2020)In several neurodegenerative disorders, the TLR/IL-1R pathways are inappropriately activated which causes a persistent level of neuroinflammation that MyD88 is proposed to mediate. In the case of Alzheimer's disease and to a lesser extent in Parkinson's disease, the aggregated proteins like amyloid-β and α-synuclein exhibit the role of DAMP and stimulate TLR on microglia as well as astrocytes. This causes MyD88 dependent signaling pathways that among other things stimulate the generation of excessive quantities of the proinflammatory cytokines like TNF-α and IL-1β. Such actions result in further neuronal injury as well as driving the disease progression. This approach to MyD88 to steer these pathways is thought to be one such strategy to alleviate the neurodegenerative pathology through the pro-inflammatory pathways.
Targeting MyD88 for the Therapeutic Development in Neurodegenerative Diseases
| Drug Name | Indication | Mechanism of Action | Key Evidence | Development Stage |
| EGCG | Alzheimer's Disease (AD) | Inhibits TLR4/MyD88/NF-κB pathway; reduces Aβ-induced microglial activation; restores mitochondrial function | Animal models: Reduced IL-6/TNF-α, improved cognition | Preclinical |
| Sinomenine | PD, AD | Downregulates TLR2/4-MyD88 signaling; inhibits NF-κB activation; reduces dopaminergic neuron apoptosis & α-synuclein aggregation | PD models: Protects substantia nigra neurons | Preclinical |
| ANX-005 | ALS | Blocks complement C1q, inhibits microglial TLR/MyD88 activation, reduces neuroinflammation | Phase II: Reduced plasma NfL; slowed disease progression | Phase II |
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 provides the entire integrated suite of services for the design of novel compounds and therapies aimed at MyD88 for neurodegenerative diseases. With advanced tools and techniques, our experienced scientists speed up the discovery and preclinical stages of development through specialized therapeutic discovery and disease model development services customized to your specifications.
MyD88-Targeted Neurodegenerative Diseases
Some neurodegenerative diseases with MyD88 involvement are of particular interest. Protheragen is actively engaged in their research and development, leveraging MyD88 pathway biology. MyD88 lies at the epicenter of the pathway relevant to Protheragen, which in turn fortifies the company's strategic understanding of neurodegenerative disorders.
Therapeutic Discovery Platform for Neurodegenerative Diseases
Protheragen's robust therapeutic discovery services encompass the entire spectrum of drug discovery and preclinical advancement, with a specific emphasis on MyD88-related targets:
Disease Models Development for Neurodegenerative Diseases
A wide array of advanced disease model development services is provided by Protheragen to ensure the precise assessment of MyD88-targeted therapeutic candidates' efficacy and safety.
Protheragen is dedicated to advancing MyD88-targeted therapeutic candidates for neurodegenerative diseases. Our end-to-end solutions offer a complete package, covering everything from target identification and disease model development to comprehensive pharmacokinetics and drug safety evaluation studies. Other focuses include investigator-initiated trials aimed at expediting the primary assessment stage.
Contact us today to explore collaboration opportunities.
References
- Wu, R., et al. “Acod1 in Immunometabolism and Disease.“ Cell Mol Immunol.17.8 (2020): 822-33. Print.
- Xiang, W., Z. Y. Chao, and D. Y. Feng. “Role of Toll-Like Receptor/Myd88 Signaling in Neurodegenerative Diseases.“ Rev Neurosc. 26.4 (2015): 407-14.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.