Iinanoparticles zeBioactive ezibuyisela i-BBB icotha isifo se-Alzheimer kwiimpuku

Un iqela lamazwe ngamazwe, kunye nobunkokeli obuvela kwiZiko le-Bioengineering yaseCatalonia (IBEC) kunye neSibhedlele sase-West China seYunivesithi yaseSichuan, iye yabonisa isicwangciso nanotechnology ukuba ibuyisela umva iimpawu ze-Alzheimer's kwiimpuku ngokulungisa umqobo wegazi ebuchotsheni (BBB). Xa sithetha ngokubanzi, imalunga sebenzisa i-nanoparticles esebenza njengeziyobisi ngokwazo ukubuyisela umsebenzi we-cerebral vascular.

Olu tshintsho kugxininiso luyavakala ukuba siyakhumbula loo nto ingqondo idla malunga I-20% yamandla kubantu abadala ukuya kuthi ga I-60% kubantwana, exhaswa yinethiwekhi exineneyo yee-capillaries apho i-neuron nganye ifumana inkxaso. Xa i-BBB itshintshiwe, inkqubo yokulahlwa kwenkunkuma iyasokola kwaye ithanda ukuqokelelwa kwe-beta amyloid (Aβ), uphawu lwesifo.Kuqikelelwa ukuba ingqondo yomntu iqulethe malunga nebhiliyoni enye yee-capillaries, ngoko ke ukubaluleka kwempilo yemithambo.

Esi sicwangciso se-nanotechnology siphakamisa ntoni?

Ngokungafaniyo ne-nanomedicine ye-classical, esebenzisa i-nanoparticles njengezithuthi nje, le ndlela isebenzisa iziyobisi ze-supramolecular ezizii-bioactive kwaye azifuni ukuthutha omnye umgaqo. Ithagethi ayiyiyo i-neuron, kodwa iBBB njengenjongo yonyango.

Kwiimeko eziqhelekileyo, I-LRP1 i-receptor iyayibona i-Aβ kwaye iyidlulisele ngaphaya komqobo kwigaziInkqubo, nangona kunjalo, ibuthathaka: Ukuba isibophelelo sigqithise okanye asanelanga, uthutho alulungelelananga kwaye i-Aβ iqokelelana. Iinanoparticles eziyilwe linganisa i-LRP1 ligands ukubuyisela olo lungelelwano.

Ngolu ngenelelo, indlela yokuphuma kwiiprotheyini eziyingxaki ezivela kwi i-parenchyma egazini, ukukhuthaza ukucocwa kwe-Aβ kunye nokusebenza komqobo oqhelekileyo. Ngokufutshane, iphinda isebenze i indlela yokucoca yendalo yengqondo.

Uvavanyo lwemodeli yezilwanyana kunye neziphumo

Uvavanyo lwenziwa kwiimpuku eziguqulwe ngokwemfuza ukuze zivelise izixa ezikhulu ze-Aβ kwaye ziphuhlise ukonakala kwengqondo. Iinaliti ezintathu zala masuntswana zazanele ukujonga utshintsho olunokulinganiswa kwii-biomarkers kunye nokuziphatha..

Ngokutsho kwababhali, iyure nje enye emva kolawulo Ukuncipha kwe-50-60% kwi-Aβ kwingqondo sele irekhodiweUkukhawuleza kwesiphumo kubonisa ukuvuselelwa ngokukhawuleza kwendlela yokuthutha kuwo wonke umqobo.

Ngaphandle kwempembelelo ekhawulezileyo, iziphumo ezihlala zihlala zichazwe. Kolunye uvavanyo, impuku eneenyanga ezili-12 yaphinda yavavanywa kwiinyanga ezili-18 kwaye yabonisa. ukusebenza okufana noko kwesilwanyana esisempilweni, ebonisa ukubuyiswa komsebenzi okuqhubekayo emva kokunyanga.

Iqela litolika ukuba kukho a chain isiphumo: ngokubuyisela umsebenzi we-vascular, Ukucocwa kwe-Aβ kunye nezinye iamolekyu eziyingozi ziphinda ziqale, kwaye inkqubo iphinda ibuyisele ibhalansi yayo.. Ngokwamazwi obunkokeli benzululwazi, amasuntswana asebenza njengechiza ivuselela indlela yokuphelisa ukuya kumanqanaba aqhelekileyo.

Iingcali zangaphandle zichaza ukufunyanwa njengento ethembisayo, nangona zichaza ukuba iziphumo zifunyenwe kwiimodeli zemurine kwaye olo guqulelo kwizigulana lufuna ukulumka. Uluntu lugxininisa imfuneko yokuqinisekisa ukhuseleko kunye nokusebenza kakuhle ebantwini ngezifundo ezingqongqo.

Ubunjineli bemolekyuli ngasemva kwe-nanoparticles

Ezi nanoparticles zikhawulwe kunye nendlela ubunjineli bemolekyuli esezantsi ukuya phezulu, ukudibanisa ubungakanani obulawulwayo kunye ne inani elichaziweyo le-ligands kumphezulu wayo ukusebenzisana nama-receptors ngendlela ethile.

Ngokumodareyitha i traffic receptor kwi-membrane, Amasuntswana alungisa kakuhle inkqubo yokudluliselwa kwe-Aβ kwi-BBBEli nqanaba lokuchaneka livula iindlela zoku lawula imisebenzi ye-receptor kude kube ngoku bekunzima ukuyilawula ngonyango.

Ngaloo ndlela, kungekhona kuphela ukupheliswa okusebenzayo kwe-Aβ kukhuthazwa, kodwa Inceda ukulungelelanisa i-vascular dynamics exhasa ukusebenza kwengqondo enempilo.. Lo ngumahluko ophambili kwiindlela ezilinganiselweyo hambisa amayeza.

Ngubani othatha inxaxheba kwaye yintoni elandelayo?

I-Consortium idibanisa kunye I-IBEC, Isibhedlele sase-West China kunye neSibhedlele sase-Xiamen saseNtshona China seYunivesithi yaseSichuan, i IYunivesithi yaseLondon, la Universidad de Barcelona, ICREA, kunye neChina Academy of Medical Sciences, phakathi kwabanye. Iziphumo zipapashwe kwijenali UTshintsho loMqondiso kunye noNyango oluJolisiweyo.

Ngokujonga inguqulelo, uhambo olunengqiqo luyahamba iziqinisekiso ezizimeleyo, Izifundo ze-Toxicological, uhlalutyo lwethamo kwaye, ukuba kufanelekile, isigaba se-I / II solingo lomntuUkhuseleko kunye nokuveliswa kwakhona kuya kuba ngundoqo ekuqhubeleni phambili.

Ngaphaya kwe-Alzheimer's, lo msebenzi ugxile kwi impilo ye-cerebrovascular njengeyona nto iphambili yesifo sengqondo esiyingozi, ukuvula intsimi yonyango ehambelana ne-classical neuron-centered approaches.

Isethi yedatha icebisa ukuba ukungenelela kwi-blood-brain barrier nge nanoparticles bioactive inokunciphisa ngokukhawuleza umthwalo we-amyloid, ukubuyisela umsebenzi we-vascular, kunye nokuphucula iziphumo zengqondo kwiigundane; indlela ethembisayo ekufuneka, ngononophelo olufanelekileyo, iqinisekiswe kuyo izifundo zeklinikhi yenziwe kakuhle.