Ikev taw qhia
Apolipoprotein Eε ApoE4 (apoE4) yog qhov muaj zog tshaj plaws ntawm caj ces muaj feem cuam tshuam rau Alzheimer's kab mob (AD). Nws ua rau muaj kev pheej hmoo ntawm kev tshaj tawm hauv Tebchaws Europe los ntawm 15 zaug, thiab nws qhov cuam tshuam rau kev pheej hmoo ntawm kev tshaj tawm hauv Asia yog ntau dua li nyob rau hauv Europe. Cov kev tshawb fawb yav dhau los tau pom tias apoE muaj txiaj ntsig zoo rau a Kev tsim thiab tshem tawm ntawm tau thiab tau nyob ntawm neurodegeneration raug cuam tshuam, tab sis nws cov txheej txheem hauv cov hlwb tseem tsis meej.
Kev tshawb fawb ntawm Boston University Lub Tsev Kawm Ntawv ntawm Tshuaj BUSM tau ua qee qhov kev cuam tshuam hauv qhov no, uas yog, apoE4 ua rau muaj kev cuam tshuam ntawm glial cell tshwj xeeb thiab tsis yog cellular autonomic regulation disorders, aggravating ad. Cov kev tshawb pom no tsis ntev los no tau luam tawm hauv phau ntawv xov xwm Cell (ntau yam cuam tshuam 66.85).
Kev tshawb fawb txog
Cov kws tshawb fawb tau tshuaj xyuas lub ntiaj teb cov ntawv sau tseg ntawm tus qauv hiPSC, tib neeg lub hlwb thiab apoE tr nas, paub meej cov yam ntxwv thiab lub luag haujlwm ntawm apoE4 noob, thiab ntxiv qhia qee cov txheej txheem ntawm apoE4 ntawm induction ntawm AD.
1. Muaj ntau hom haplotypes uas muaj apoE loci nyob ntawm APOE genotype.
2. Cov txheej txheem tswj hwm lossis qhov chaw nyob ze ntawm apoE sib txawv ntawm hom mus rau hom, thiab lipid metabolic tsis ua haujlwm yog tshwj xeeb rau tib neeg apoE4 glial hlwb (cell-specific disorder).
Stromal ntsig txog, ECM ntsig txog, interferon thiab cytokine signaling txoj hauv kev hauv nas microglia thiab astrocytes, tab sis tsis muaj kev ua haujlwm ntawm lipid ntsig txog kev mob.
3. ApoE4 microglia thiab astrocytes ua rau lipid metabolism tsis meej thiab inflammatory stromal teeb meem, uas txhawb ib leeg, ua rau aggravation ntawm AD.
ApoE4 tuaj yeem tsav lysosomal cholesterol chelation hauv astrocytes, nce cov roj cholesterol biosynthesis thiab txo cov efflux, nws thiaj li ua rau lipid tsis txaus.
ApoE4 induces proinflammatory stromal disorders (tsis yog cellular autonomic disorders) los ntawm astrocyte neuron kev sib txuas lus, exacerbating lipid teeb meem nrog rau cholesterol biosynthesis thiab txo efflux.
ApoE4 inhibits microglia apoe-trem2-plc 2 teeb liab transduction. Kev txo qis ntawm apoe-trem2 teeb liab hloov pauv hauv microglia yuav ua rau kom qhov tsis sib xws ntawm lipid metabolism thiab inflammatory xeev.
Cov ntsiab lus
Txoj kev tshawb no qhia txog tib neeg qhov tshwj xeeb ntawm apoE4 thiab hom kev hloov pauv ntawm tes thiab phenotype ntawm AD hlwb hlwb, qhia txog qhov tsis xws luag ntawm lipid homeostasis thiab glial activation. Qhov no qhia tau hais tias nyob rau hauv apoE4 cov neeg nqa khoom, kho cov glial lipid homeostasis thiab tswj kev mob tuaj yeem dhau los ua ib txoj hauv kev tshiab rau kev kho AD. Cov kev tshawb fawb kuj tau lees paub tias LXR (lub siab X receptor) agonists tuaj yeem txuag cov dysregulated lipid / cholesterol metabolism hauv ApoE 4 astrocytes thiab rov ua kom cov efflux mus rau apoE3 (ib txwm noob).