Studies On The Effects Of Selenoprotein SELENOK And Total Lotus Plumule Alkaloids For The Prevention And Cure Of Alzheimer's Disease

Alzheimer's Disease?AD?,commonly known as senile dementia,is a progressive neurodegenerative disease with insidious onset.Previous researches found that selenium,a trace element,has the ability to prevent AD.The role of selenoprotein SELENOK in preventing AD needs to be determined by animal experiments.Some scholars consider that AD is a neuroinflammatory disease.So whether total lotus plumule alkaloids?LPAs?,which have anti-inflammatory effects,can ben used in AD therapy and whether this function is related to SELENOK are also needed to be determined by animal experiments.On the basis of obtaining SELENOK knockout mice by crispr-cas9 technology,the function and mechanism of selenoprotein SELENOK in preventing the occurrence of AD were studied by comparison the difference of the following performances of SELENOK knockout pure syncytic mice and the same group of SELENOK normally expressed mice after the induction of AD by brain injection of AlCl₃ or or A?_1-42.The changes of the abilities of learning and memory of the SELENOK knockout mice were detected by Morris test,the changes of A?deposit formation and activated microglial cells in brain tissue were detected by Congo red staining,immunohistochemical staining and immunohistochemical fluorescence staining of brain tissue paraffin sections,the changes of neurofibrillary tangles?NFTs?formation and lesion of neurons were detected by glycine silver dip staining and hematoxylin eosin?HE?staining of tissue paraffin section and the changes of some related proteins in brain tissues were studied by western blot.It was found that,compared with SELENOK normally expressed mice,the escape latency of SELENOK knockout mice was prolonged and the time around the platform was decreased after the induction of AD by AlCl₃ or A?_1-42,especially A?_1-42,indicating that SELENOK can partially prevent the decline of learning and memory abilities of the mice caused by AD.The amount of A?deposits in the brain tissue of SELENOK knockout mice were significantly increased and the number of activated microglial cells was significantly decreased after the injection of AlCl₃ or A?_1-42,indicating that SELENOK may decrease the production of A?deposits by increasing the number of activated microglial cells in the brain of mice.The formation of NFTs and lesion of pyramidal cells in hippocampal tissue of SELENOK knockout mice were significantly increased,revealing that SELENOK can inhibit the generation of NFTs and lesion of neurons.Western Blot showed that the expression of phosphorylated Tau protein,the key protein that causes the formation of NFTs,was significantly increased in the brain tissue of SELENOK knockout mice after the induction of AD.It is speculated that selenoprotein SELENOK may play an important role in preventing AD by inhibiting the generation of NFTs through preventing the phosphorylation Tau protein.After 28 days of gastric administration of total lotus plumule alkaloids?LPAs?in APP/PS1 mice aged 6 months,the feasibility of using LPAs for AD therapy was studied through similar experiments as above.It was found that the learning ability of the APP/PS1 mice was significantly increased compared with the untreated mice.Excessive activation of microglial cells after AD is one of the major factors contributing to neuroinflammation.It was found that the A?deposits in hippocampus and cortex are significantly reduced and the number of activated microglial cells is significantly dercreased after the administration.The NFTs generation and lesion of hippocampus pyramidal cells and cortex were significantly reduced after administration.Western blot results showed that the expression of phosphorylated Tau protein and Calpain in brains of the administrated group was significantly decreased and the expression of selenoprotein SELENOK was significantly increased.Through the above studies,it can be proved that LPAs,mainly composed by dibenzylisoquinoline alkaloids,do have certain therapeutic effects of AD.The effects may be caused by their anti-phosphorylation of Tau protein and may be related to their effect on the elevated expression of SELENOK by inhibiting the expression of Calpain,since SELENOK is one of the enzyme cutting targets of Calpain.