Aß can induce activation of microglia and astrocyte to secret pro-inflammatory cytokines, which can promote neuroinflammation and neurodegeneration. We are currently testing several factors that can modulate neuroinflammation to modulate the progression of Alzheimer’s disease (AD).
CLEC5-A
Microglia, the resident macrophage in the central nerve system, mediates the immune responses, synaptic plasticity, cognition, and diseases. The activation of microglia and its receptors contributes to AD pathology. C-type lectin domain family 5 member A (CLEC5A), one of C-type lectin receptors on microglia has been shown to play a crucial role in brain inflammatory disease. Thus, we are interested in whether CLEC5A may mediate Aβ-induced neuroinflammation and contribute to AD pathogenesis. Our preliminary results suggest that Clec5a knockout can improve learning and memory in APP transgenic mouse model. Next, we will examine the mechanism of how CLEC5A regulates learning and memory in APP transgenic mice. If CLEC5A indeed plays an important role in AD pathogenesis, this could be a novel therapeutic target in the future.
Functional modulation of DcR3 on innate-immune system in the brain
Inflammation is considered to be prominent through entire AD progression, and more evidence showed the interaction between innate-immune system and neuron circuits contributes to amyloidogenesis, synaptic plasticity, and finally memory loss. We aim to work on modulating CNS inflammatory environment by generating APP/DcR3 double transgenic mice and in vitro cell culture. We characterize diversity effects in CNS through different subtypes of activated microglia. There are increased M1 inflammatory microglia and cytokine-induced neurotoxicity in AD mice brain, whereas DcR3 prevents neuronal loss by switching the CNS environment into anti-inflammatory status and down-regulating cytokine-induced neurotoxicity. We propose the microglia-neuron network can be a potential target for AD treatment.