Regulation Of Autophagy Effected By PS1 Mutations In Alzheimer’s Disease

Alzheimer’s disease is a kind of progressive degenerative disease of nervous system.Clinically,performing as memory impairment,aphasia,apraxia,agnosia,visual spatial skills damage,executive dysfunction,and changes in personality and behavior,so on.And β-amyloid plaques is one of the pathological features of this disease,which is closely related to presenilin1(PS1)mutaions.On the one hand,autophagy is a pathway of cleaning toxic protein.Microtubule-associated protein 1 light chain relationships 3(LC3)gene has an important effect on it.On the other hand,studies show that PS1 mutations affect autophag y.A number of mutations would reduce the level of autophagy.In the early-onset familial Alzheimer’s the most common form of disease,the mutant PS1 genes dir ectly hampered by lysosomal proteolysis to destroy autophagy.while in another form of Alzheimer’s disease,autophagy barrier function may be associated with various genetic or environmental factors.This paper explores PS1 mutations and microtubule-associated protein 1 light chain relationships 3(LC3)genes.The experiments include : getting the c DNA template,LC3 cloning and eukaryotic expression,transfection of five PS1 mutations gene into the 20E2 cells,detecting changes of protein expression.In order to determine the interaction between LC3 and PS1 mutaions,discuss the possibility of using autophagy mechanism to verify treatment.My research get the following results :1)Getting LC3 cloning with the template from U251 cells.A nd construct the eukaryotic expression vector of LC3;2)PS1 mutation may reduced autophagy levels.Many evidence proof that autophagy can be a potential therapeutic strategy to AD,the future can continue to explore the possibility of interference autophagy gene PS1 mutation.