Inflammation/Infection Targeting Therapies Study
Background of Inflammation/Infection Targeting Therapies Study
Alzheimer's disease (AD) is the most prevalent progressive neurodegenerative disorder. The pathology of AD is a long process with a series of problems associated with aging, including immune system alterations, elevated levels of pro-inflammatory cytokines, increased leakage from the gut, and dysbiosis as well as the emergence of senescent cells in the gut and brain. Recently, the traditional AD pathogenesis based on amyloid-beta (Aβ) and neurofibrillary tau tangles has been challenged by the "antimicrobial protection hypothesis". The mechanisms of action (MoAs) in AD based on the inflammation and infection present a perspective opportunity for innovative therapeutic approaches by treating the inflammation and infection or regulating the immune system. Creative Biolabs provides thereby a variety of reliable in vivo, in vitro, and ex vivo assays enabling researchers to inquire into the pathogenesis of AD associated with inflammation and infection and develop anti-inflammatory therapies for AD.
Inflammation and Infection MoA in AD
The pathological hallmarks of AD are usually considered to be extracellular Aβ plaques and intracellular aggregation of neurofibrillary tau tangles due to the insufficient microglial phagocytic capacity. Soluble pathologic Aβ and tau will activate glia in a downstream response, releasing multiple pro-inflammatory cytokines that trigger neuroinflammation. Aβ oligomers can activate microglia by binding to Aβ receptors such as LRP1, TLR4, and CD36, releasing proinflammatory cytokines such as IL-1β, IL-6, IL-8, and TNF-α. Amyloid precursor protein (APP) production is increased by those cytokines, which cleavage into increased amount of Aβ. Aβ oligomers directly or indirectly activate astrocytes through cytokines inducing inflammatory response and impairing neurons. Pathologic tau species can activate microglia via NF-κB and NLRP3 inflammasome pathways releasing cytokines. Another possible pathogenic mechanism of AD is based on microbial infection-triggered neuroinflammation in the central nervous system via gut-brain axia that leads to neurodegeneration and senescence of the immune cells. In addition, Aβ may have a neuroprotective function against pathogens in the early stage of infection.
Fig.1 Possible intervention checkpoints according to the infection hypothesis. (Fülöp, 2020)
What Can We Do for You?
Creative Biolabs is devoted to providing a series of inflammation and infection targeting therapies study services to content your research and preclinical drug development requirements. The assays used to study inflammation and infection targeting therapies in AD mainly focus on the microglia and astrocytes, including cytokine release assay, lipopolysaccharide (LPS)-induced inflammation assay, and nitric oxide production assay. Our scientific team established a full range of cell models and animal models as well as high throughput imaging platform and advanced electrophysiology technique that enable accurate data for the assays. Researchers could therefore utilize the data for further studies and explore novel therapies for AD. Please don't hesitate to contact us for further information.
Reference
- Fülöp, T.; et al. Targeting infectious agents as a therapeutic strategy in Alzheimer's disease. CNS drugs. 2020, 34(7): 673-695.
