Iqembu lamazwe ngamazwe likukhombisile lokho imijovo emithathu yama-nanoparticles e-bioactive ingahlehlisa izimpawu ze-Alzheimer's kumagundane ngokuvuselela umgoqo wegazi nobuchopho, isango lokulawula imithambo yobuchopho. Ngokusho kwababhali, ngesikhathi sokuphatha, a 50-60% ukwehla kwe-amyloid-β esicutshini sobuchopho.
Ucwaningo, oluqondiswe ngabakwa I-Institute of Bioengineering of Catalonia (IBEC) futhi i Isibhedlela sase-West China yaseSichuan University, ishicilelwe kujenali Ukuguqulwa Kwesiginali kanye Nokwelashwa OkuhlosiweNakuba imiphumela imangalisa, labo abanomthwalo wemfanelo bayakugcizelela lokho Lawa amamodeli ezilwane nokuthi noma yisiphi isicelo somtholampilo sizodinga izinyathelo ezengeziwe.
Lelisu liletha ini
Ngokungafani neningi le-nanomedicine yakudala, lapha izinhlayiya aziyona imoto elula: sebenza njengezidakamizwa ze-supramolecular ngomsebenzi wayo. Umgomo awukona ukuhlasela i-neuron ngokuqondile, kodwa buyisela umgoqo wegazi ebuchosheni (BBB) ukuze uhlelo lwe-vascular ngokwalo lukwazi ukubuyisela umsebenzi walo wokuhlanza.
Ubuchopho buyisitho esidinga kakhulu ngokubuka okunamandla, budla nxazonke Amaphesenti angu-20 wamandla kubantu abadala futhi ingafinyelela ku-60% ezinganeni. Lesi sidingo sisekelwa inethiwekhi ye-capillary eminyene ngokungavamile: kulinganiselwa ukuthi ilandelana ama-capillary ayizigidigidi ukuchelela nokondla ama-neurons.
Lapho i-BBB yehliswa, ukuqedwa kwezinhlanganisela eziyingozi konakala. Ngokugxila ku lungisa lesi sikhombimsebenzisi, ukwelapha kusiza ukuwela amaprotheni angcolile egazini, lapho umzimba ungawaqeda ngokujwayelekile.
Esimeni se-Alzheimer's, okuhlosiwe okuyinhloko yi- i-amyloid-β (Aβ), ukunqwabelana kwayo kushintsha ukuxhumana kwe-neuronal futhi kuhlotshaniswa nokuwohloka komqondo okuqhubekayo.
Isebenza kanjani: I-BHE kanye nendlela ye-LRP1
Ngaphansi kwezimo zomzimba, amaprotheni I-LRP1 Kuwukhiye ekuboneni i-Aβ nokuyihambisa inqamule i-BBB iye egazini. Kodwa-ke, lolu hlelo lubucayi: uma ukubophezela kunamandla kakhulu futhi kukhulu, izitebhisi zezokuthutha kanye ne-LRP1 iyancipha; uma ibuthakathaka, isignali ayanele ukwenza inqubo isebenze.
Ama-nanoparticles aklanyelwe alingisa i-LRP1 ligands futhi anikeze a ukusebenzisana okuningi okuthuthukisa ukudlula kwe-Aβ ngaphandle kokugoqa isistimu. Ngale ndlela, umzila wemvelo wokuphuma uyavuselelwa futhi umthwalo onobuthi uyancipha ku-parenchyma yobuchopho.
Ithimba liqashe a ubunjiniyela bamangqamuzana aphansi phezulu, ngokunembile ukulawula i usayizi wezinhlayiyana kanye nenani lama-ligands ebusweni bayo. Lokhu kulungiswa kahle kuvumela ukushintshwa kwe-membrane receptor traffic kanye nokuqondisa impendulo yebhayoloji ngokucaciswa okukhulu.
Ngokusho kwababhali, ukubuyiselwa kwe-vasculature kubangela umphumela ihlasele: Ngokususa i-Aβ namanye ama-molecule ayingozi, i-BBB ithola ibhalansi futhi ubuchopho ngokwabo buqala kabusha i-homeostasis yabo.
Idizayini yokufunda kumagundane
Ukuhlola i-hypothesis, sisebenzise amagundane ashintshashintshayo ngokukhiqiza ngokweqile kwe-Aβ kanye nokuphazamiseka kwengqondo okumakiwe. Iphrothokholi yayihlanganisa ukuphathwa kwe imithamo emithathu yezidakamizwa ze-supramolecular kanye nokuqapha okusebenzayo kanye ne-biochemical izinyanga.
Ingqophamlando yokuqala kwaba ngokushesha: at the isikhathi somjovo Ukwehliswa ngo-50-60% kumazinga e-Aβ ebuchosheni kutholiwe. Kamuva, ekuhlolweni kwenkumbulo nokuziphatha, izilwane zabonisa ukuthuthuka okuqhubekayo.
Emfanekisweni, igundane Izinyanga ze-12 (cishe okulingana neminyaka engama-60 kubantu) bathole ukwelashwa futhi, ezinyangeni eziyisithupha kamuva, ukuziphatha kwayo kwakufana nokwegundane elinempilo, naphezu kokuthi kakade isisesigabeni esithuthukile (izinyanga ezingu-18).
Ababhali bagcizelela ukuthi lokhu kulingana kweminyaka kuyinkomba nokuthi, njengesinyathelo sokuzivikela, akufanele ikhishwe ngaphandle ngqo kubantu ngaphandle kokuhlolwa okuthile.
Obani abasayiniwe nokuthi yashicilelwa kuphi
Le phrojekthi iqondiswe ngokubambisana yi-IBEC (Barcelona) kanye neSibhedlela saseWest China saseSichuan University, ngokubamba iqhaza UCL kanye namaqembu avela e-United Kingdom nase-China, kanye nabacwaningi abaxhumene ne Universidad de Barcelona kanye ne-ICREA.
Umsebenzi uvela ku Ukuguqulwa Kwesiginali kanye Nokwelashwa Okuhlosiwe ngaphansi kwesihloko kugxilwe ku- ukuguquguquka ezokuthutha eziningi ngaphesheya kwe-BBB. Inkomba ye-athikili (i-DOI) ebikwe ababhali ithi 10.1038/s41392-025-02426-1.
Imiphumela kanye nezinyathelo ezilandelayo
Imiphumela ivula a indlela ethembisayo ukubhekana neminikelo ye-vascular ye-Alzheimer's futhi ingahambisana nokwelashwa okwamanje okubambezela ukwehla. Nokho, ukuthuthela emtholampilo kudinga khombisa ukuphepha nokusebenza ngempumelelo kubantu.
Ochwepheshe abangaphandle kocwaningo baqaphile: kuyintuthuko enkulu, kodwa eyandulelayoUkukhiqiza kabusha kuzodingeka kuqinisekiswe, umthamo kanye neshejuli ilungiswe, kanye nemiphumela yesikhathi eside engaba khona ifundwe ngaphambi kokucutshungulwa kwezilingo zesiguli.
Uma izigaba ezilandelayo ziqinisekisa lokho okuye kwabonwa, le ndlela ingakwazi ukucabanga kabusha ngezokwelapha I-Alzheimer's ngokugxila ku-BBB njengohlelo lokuhlanza hhayi nje ekuhlaseleni i-amyloid plaque ngqo.
Idatha iphakamisa ukuthi ukulungisa isithiyo sobuchopho begazi ngama-nanoparticles aklanywe ngokwezifiso kunganciphisa ngokushesha i-amyloid-β, kubuyisele ukusebenza kwengqondo kumagundane, futhi kuqalise umphumela wokudansa. iqinisa i-vasculature; umugqa womsebenzi onamandla, kodwa ongakaqedi ngokugcwele indlela yokulawula kanye neyomtholampilo.