Regulation Of Kainie Acid On Microglia In Different Inflammatory States

Alzheimer's Disease(AD),was found in 1907,is one of the most common type of neurodegenerative diseases,and about 50%of people with dementia are diagnosed with Alzheimer' s disease.Until now,approximately 50 million people worldwide have Alzheimer,s disease,and the number has increased with life expectancy increased.Currently,the drugs used for the treatment of Alzheimer' s disease can only delay the development of the disease but cannot completely cure AD.We already know that neuroinflammatory response plays an important role in the development of Alzheimer's disease,and the different stages of the disease correspond to different neuroinflammatory responses.Congenital immune sentinel microglia in the central nervous system are rapidly activated from resting state to anti-inflammatory and pro-inflammatory phenotypes in response to cell damage,respond to inflammation,release inflammatory factors,eliminate damage Cells and remove metabolites.We have known that in the early stages of AD(pre-clinical stage),activated microglia are primarily M2 phenotypes that play a neuroprotective and anti-inflammatory role;in the later stages of AD(clinical stage),microglia become a pro-inflammatory Ml phenotype..In the brain of AD patients,the levels of cytokines secreted by microglia continue to increase,including:IL-6,TNF-?,IFN-?.These cy tokines cause neuronal death and play an important role in the progression of AD.Most of the research on Alzheimer' s disease is applied to neurons.In view of the research,the microenvironment changes in the brain at various stages of Alzheimer's disease are complicated,and the microglia changes at different stages of the disease.To the dual role of protection and injury,ion-type glutamate receptors are found in microglia,opening a new direction in microglia phenotypic regulation research.In this study,we studied the regulation of sea salt alginic acid against microglia in inflammation and pro-inflammatory state from the aspects of proliferation,toxicity and cytokine secretion level,thus providing a basis for the treatment of Alzheimer' s disease.The results showed that the cell viability,toxicity and secretion of various cytokines did not change significantly when the unactivated microglia were stimulated with the ionotropic glutamate receptor agonist.When KA is used to stimulate microglia that are already in the M2 phenotype,it causes a significant decrease in IL-4 and IL.10 levels.When KA was used to stimulate microglia that were already in the Ml phenotype,the secretion levels of IFN-?,TNF-?,and IL-6 were significantly decreased.Therefore,we can infer that the use of KA blockers will have a positive effect on early AD treatment;because the KAR receptor is similar to the AMPAR receptor mechanism,perhaps AMPAR receptor agonist blockers can also be used to the same effect.In addition,although KA also has a positive effect on Ml type microglia in advanced AD,due to the strong neurotoxicity of KA,we do not consider directly treating KA with AD or its analogues,but should use Targeting receptor agonists against microglia,which can prevent the damage of neurons and achieve therapeutic effects.