Kev Ntsuam Xyuas Ntawm Cov Kabmob Neurodegenerative Feem Ntau: Txoj Kev Kho Mob Tam Sim No Thiab Lub Luag Haujlwm Ntawm Nanotherapeutics Part 2
Jun 27, 2024
3.1.2. Cholinesterase Inhibitors
Tam sim no, cholinesterase inhibitors yog thawj kab tshuaj noj rau AD. Donepezil, rivastigmine, thiab galantamine yog peb lub ntsiab cholinesterase inhibitors siv kho mob.
Nyob rau hauv xyoo tas los no, tus naj npawb ntawm AD (Alzheimer's disease) cov neeg mob tau nce ntxiv, thiab tus kab mob no muaj kev cuam tshuam zoo rau cov neeg mob lub neej. Ntxiv nrog rau qhov pom tseeb tshaj plaws kev paub tsis meej thiab kev txawj ntse degeneration, nco tsis tau kuj yog qhov teeb meem txhawj xeeb tshaj plaws rau cov neeg mob. Yog li ntawd, kev sib raug zoo ntawm AD kev kho mob thiab kev nco tau txais kev saib xyuas thoob plaws.
Ua ntej, cia peb saib vim li cas cov neeg mob AD lub cim xeeb poob. AD yog ib qho kev hloov pauv ntawm lub hlwb, ib qho ntawm cov laj thawj tseem ceeb tshaj plaws uas yog neuronal lwj. Raws li tus kab mob maj mam zuj zus, neurons hauv lub hlwb maj mam tuag, ua rau txo qis qhov tseeb thiab ceev ntawm cov teeb liab kis tau tus mob, thiab yog li ntawd, tus neeg mob lub cim xeeb kuj yuav cuam tshuam. Txawm li cas los xij, kev sib raug zoo ntawm kev kho AD thiab kev nco kuj ua rau peb muaj kev cia siab. Txawm hais tias peb tsis tuaj yeem kho AD ncaj qha nrog tshuaj, peb tuaj yeem txo nws cov tsos mob los ntawm kev siv tshuaj thiab kev kho mob. Piv txwv li, kev kho tshuaj tam sim no tau zoo heev, thiab qee cov tshuaj tuaj yeem txhim kho cov neeg mob lub peev xwm kev txawj ntse, kev xav, thiab kev xav, thiab tseem txhawb kev loj hlob ntawm neurons.
Ntxiv nrog rau kev kho tshuaj, qee qhov kev kho mob tsis yog tshuaj muaj txiaj ntsig. Piv txwv li, los ntawm kev paub txog tus cwj pwm kev coj cwj pwm (CBT) thiab kev coj cwj pwm kev coj cwj pwm (BT), peb tuaj yeem hloov kho cov neeg mob tus cwj pwm coj tus cwj pwm thiab kev paub txog tus cwj pwm, xws li tsim kom muaj ib qho kev npaj ua si uas muaj txiaj ntsig zoo rau lub cev noj qab haus huv thiab siv kev ua si thiab kev txawj ntse los txhawb cov hlwb thiab txhim kho kev nco.
Tsis tas li ntawd, qee qhov kev tshawb fawb kuj tau pom tias kev noj zaub mov thiab kev tawm dag zog tuaj yeem ua lub luag haujlwm hauv kev kho AD. Qee cov khoom noj uas nplua nuj nyob hauv antioxidants, xws li blueberries thiab txiv ntseej, tau pom tias tiv thaiv kev puas tsuaj rau cov paj hlwb. Kev tawm dag zog lub cev kom zoo kuj tuaj yeem txhawb kev loj hlob neuron thiab ua rau lub cev metabolic nce ntxiv.
Hauv cov ntsiab lus, kev sib raug zoo ntawm kev kho AD thiab kev nco yog ua tiav. Ntxiv nrog rau kev pabcuam ncaj qha, qee qhov kev siv tshuaj tsis yog tshuaj kuj tuaj yeem ua lub luag haujlwm zoo. Txawm hais tias AD muaj kev cuam tshuam zoo rau cov neeg mob lub neej, peb tseem yuav tsum muaj tus cwj pwm zoo, muab cov neeg mob saib xyuas thiab txhawb nqa ntxiv, pab lawv rov tsim kho thiab tswj lawv lub peev xwm nco, thiab txhim kho lawv lub neej zoo. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco. Cistanche tuaj yeem txhim kho kev nco zoo vim Cistanche muaj cov tshuaj tiv thaiv antioxidant, tiv thaiv kab mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidation thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv ntawm lub paj hlwb. Tsis tas li ntawd, Cistanche tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm muaj peev xwm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv qhov tshwm sim ntawm kev paub tsis meej thiab cov kab mob neurodegenerative.
Nyem paub txoj hauv kev los txhim kho lub hlwb
Hauv AD, muaj kev cuam tshuam ntawm cholinergic neurons thiab kev poob qis hauv qhov ntau ntawm acetylcholine hauv thaj tsam cortical ntawm lub hlwb. Ntau qhov kev tshawb fawb tau nthuav tawm tias qhov nce ntxiv ntawm acetylcholine hauv cov neeg mob demented pab txo qis kev txawj ntse. Cholinesterase inhibitors txwv acetylcholine degradation, thiab cov neeg mob tau txais txiaj ntsig los ntawm kev ua haujlwm cholinergic ntxiv [55].
Tacrine yog thawj choline esterase inhibitor pom zoo rov qab rau xyoo 1993 los ntawm FDA tab sis raug txiav tawm tom qab vim nws cuam tshuam txog hepatotoxicity. Donepezil yog siv rau me me-rau-nruab nrab AD thiab muab raws li cov ntsiav tshuaj ntawm qhov ncauj ntawm 5 lossis 10 mg / hnub. Tsis ntev los no, cov koob tshuaj ntau dua ntawm donepezil (23 mg / hnub), ib leeg lossis ua ke nrog memantine, tau pom zoo rau cov neeg mob nruab nrab-rau- mob hnyav.
Lwm acetylcholinesterase inhibitorused rau me me-rau-mob AD yog rivastigmine. Tsis zoo li lwm cov cholinesterase inhibitors, rivastigmine muaj nyob rau hauv ib qho kev hloov pauv thiab inhibits acetylcholinesterase thiab butyrylcholinesterase enzymes. Galantamine, chav kawm tom ntej ntawm cholinesterase inhibitors, tau pom zoo rau me me-rau-nruab nrab AD ntawm ib koob tshuaj ntawm 16-24 mg / hnub.
Dhau li ntawm nws cov nyhuv inhibitory ntawm cholinesterase kev ua, nws kuj tsim allosteric modulation ntawm nicotiniccholinergic receptors [56].Txawm hais tias ntau cov tshuaj tau tsim rau AD, cholinesterase inhibitors tseem yog tib txoj kev xaiv muaj rau cov neeg mob. Cov tshuaj tsis ntev los no pom zoo aducanumab yog qhov tsis txaus ntseeg hauv nws cov txiaj ntsig thiab exorbitant hauv tus nqi.
Txawm li cas los xij, cholinesterase inhibitors qhia qhov ua tau zoo. Lawv ua tiav qhov kev txhim kho me me hauv cov neeg mob lub peev xwm kev txawj ntse, thiab lawv tau sau npe tias yog kev kho mob cov tsos mob ntau dua li hloov pauv pathology [57].
Ntxiv mus, cov lus nug muaj nyob rau seb cov tshuaj tam sim no puas tuaj yeem hla BBB cov koob tshuaj tseem ceeb los ua kom cov txiaj ntsig xav tau.
3.1.3. Glutamate Regulators
Glutamate yog qhov tseem ceeb excitatory neurotransmitter hauv lub hlwb. Los ntawm kev ua haujlwm ntau dhau hauv postsynaptic neurons xws li NMDA receptors, glutamates confer neuronaldamage, ua rau neurodegeneration.
Txawm li cas los xij, ua tiav inhibition ntawm NMDA receptorshas ua rau muaj kev phiv loj heev. Yog li ntawd, memantine, ib qho tsis sib tw NMDA receptor antagonist, tau tsim, uas muab cov txiaj ntsig zoo nrog NMDA receptoractivation thiab tseem tiv thaiv cov neeg mob los ntawm inhibitory cuam tshuam vim overactivation [58].
Memantine tau pom zoo nyob rau xyoo 2003 rau cov neeg mob nruab nrab-rau-mob AD ntawm koob tshuaj 5-20 mg / hnub. Monotherapy ntawm memantine tau txais txiaj ntsig zoo rau cov neeg mob AD nrog kev paub zoo dua ntawm cov placebo.
Hauv kev sib xyaw ua ke nrog acetylcholinesterase inhibitors, kev sim tshuaj ntsuam xyuas tau pom tias muaj txiaj ntsig zoo rau ib xyoos dhau los ntawm kev kho mob monotherapy [59,60]. Txawm li cas los xij, chav kawm ntawm cov tshuaj no tseem tsis tau hais txog cov kab mob ntawm AD thiab feem ntau yog siv los txo cov tsos mob.
3.2. Txoj Kev Kho Mob rau PD
Txawm hais tias PD yog qhov thib ob feem ntau ND, muaj qhov tsis muaj kev kho mob uas tshwj xeeb tshaj yog hloov cov kab mob pathophysiology. Hloov chaw, qee qhov kev xaiv hais txog cov tsos mob ntsig txog lub cev muaj zog thiab cov tsos mob tsis yog lub cev muaj zog sib cais rau cov tsos mob ntawm cov neeg mob.
Txoj hauv kev tseem ceeb hauv kev tswj hwm PD yog txhawm rau ntxiv qhov txo qis dopamine qib hauv thaj tsam substantia nigra ntawm lub hlwb. Ntau txoj hauv kev tau muab tso rau hauv qhov chaw uas lub hom phiaj los ua kom cov qib dopamine ntxiv.
Txoj kev kho ntau tshaj plaws yog kev sib xyaw ntawm levodopa thiab carbidopa. Levodopa yog ib qho ua ntej ntawm dopamine uas pab kho lub cev muaj zog uas ua rau poob ntawm dopamine. Carbidopa yog ua ke nrog levodopa los tiv thaiv qhov kev puas tsuaj peripheral ntawm levodopa ua ntej nws mus txog lub hlwb.
Tsis tas li ntawd, entacapone thiab tolcapone kuj tseem siv los tiv thaiv methylation oflevodopa los ntawm catechol-O-methyl transferase (COMT), yog li tiv thaiv levodopaloss los ntawm methylation.
Dopaminergic agonists xws li apomorphine hydrochloride, pergolide, pramipexoledihydrochloride, ropinirole hydrochloride, thiab rotigotine, uas tsim ib qho zoo tib yam effectto dopamine, kuj muaj rau kev kho mob ntawm PD. Monoamine oxidase inhibitors yog cov chav kawm tom ntej ntawm cov tshuaj muaj. Lawv inhibit oxidative deamination ntawm dopamine nyob rau hauv lub hlwb thiab tiv thaiv dopamine poob.
Selegiline thiab rasagiline yog ob qho piv txwv ntawm monoamine oxidase inhibitors [39] .PD yog txuam nrog cov tsos mob tseem ceeb (MNMS) zoo li tag nrho cov NDs, suav nrog kev nyuaj siab, kev puas siab puas ntsws, pw tsis tsaug zog, cem quav, dementia, thiab olfactory deficit, thiab lawv raug kho mob symptomatically [61 ].
Rivastigmine, donepezil, thiab galantamine raug tshuaj kom txo qis cov tsos mob ntsig txog dementia. Clozapine, quetiapine, thiab pimavanserinare pom zoo cov tshuaj rau kev kho cov tsos mob ntsig txog kev puas siab puas ntsws. Kev siv melatoninor clonazepam yog pom zoo rau cov tsos mob ntawm kev pw tsaug zog [62].
3.3. Txoj Kev Kho Mob rau ALS
ALS yog tus kab mob neuron lub cev muaj zog uas ua rau pom cov tsos mob ntawm frontotemporal dementia, kev hloov ntawm tus cwj pwm, thiab kev paub tsis meej nrog kev loj hlob ntawm tus kab mob.
ALS cov neeg mob succumb ua pa tsis ua hauj lwm thiab tuag nyob rau hauv peb mus rau tsib xyoos ntawm cov tsos mob tshwm sim [63]. Muaj ob cov tshuaj pom zoo rau cov neeg mob ALS, piv txwv li, riluzole thiab edaravone. Riluzole, glutamate-receptor antagonist, tau pom zoo rov qab rau xyoo 1995 ua ib ntsiav tshuaj ntawm qhov ncauj nrog koob tshuaj 100 mg / hnub.
Kev sim tshuaj ntsuam xyuas tau pom tias riluzole siv lub neej ntawm ALS cov neeg mob los ntawm 3 mus rau 4 lub hlis piv rau cov placebo pab pawg.
Edaravone, ib tug dawb-radical scavenger, tsis ntev los no tau pom zoo nyob rau hauv 2017 raws li ib tug intravenous infusion nrog adose ntawm 60 mg / hnub, thiab nws yuav pab ncua kev loj hlob ntawm tus kab mob [64]. Dhau li ntawm cov tshuaj no, cov neeg mob tau kho cov tsos mob kom txhim kho lawv lub neej zoo. Tsis muaj ib qho kev kho mob-kho kho mob muaj nyob rau tam sim no.
4. Cov Kev Nyuaj Siab ntawm Kev Xa Khoom Siv Hluav Taws Xob
Txoj kev kho tam sim no rau kev tswj hwm ntawm NDs tau pab tswj kev kis tus kab mob ntau dua li tshem tawm cov hauv paus hauv paus. Qhov teeb meem ntawm neurodegeneration nyob tom qab BBB, thiab qhov ntawd yog qhov uas feem ntau ntawm cov qauv no tsis ua tiav.
Qhov tsis muaj peev xwm thauj cov koob tshuaj txaus rau lub hlwb txwv txoj kev cuam tshuam zoo ntawm NDs. Qhov zoo tshaj plaws ntawm BBB, nrog rau qhov tsis zoo permeative potency ntawm feem ntau, yog tias tsis yog txhua yam tshuaj, suav nrog qhov tsis muaj kev kho mob tsim nyog rau NDs.
4.1. Ntshav-Brain Barrier (BBB)
BBB tau raug piav qhia tias yog ib qho kev cuam tshuam uas tiv thaiv cov khoom hauv cov ntshav los ntawm kev nkag mus rau hauv lub hlwb, tso cai rau kev saib xyuas ntawm homeostasis thiab lub hlwb ua haujlwm tsis zoo [65].
Cov hlwb sib txawv hauv lub hlwb (lub hlwb microvascular endothelial hlwb, nruj junctions, neurons, astrocytes, thiab basal daim nyias nyias) fuse los tsim kom muaj lub cev nruj nreem hlwb hauv BBB [66]. Qhov tsis muaj fenestrations nyob rau hauv lub hlwb capillary endothelialcells txwv qhov diffusion ntawm me me molecules thiab proteins [67,68].
Cov kab mob endothelial txuas ntxiv mus rau qhov cuam tshuam tsis tu ncua los ntawm kev sib tshuam ntawm endothelial junctions, txwv tsis pub thauj cov dej-soluble tshuaj [69,70]. Tsis tas li ntawd, cov hlwb endothelial nyob ib puag ncig los ntawm basal lamina, astrocytes, thiab pericytes, txwv kev nkag mus rau cov tshuaj molecules los ntawm cov ntshav mus rau lub hlwb [71].
Lub zog ntawm qhov teeb meem no yog qhuas los ntawm efflux transporters nyob rau hauv lub hlwb capillary, thiab cov transporters rov qab cov khoom uas nkag mus rau lub hlwb rov qab mus rau hauv cov hlab ntsha [72]. Tsis tas li ntawd, lub permeability muaj nuj nqi ntawm BBB yog ntxiv tswj los ntawm internet-endothelial junctions, uas yog protein complexes nrog rau nruj junctions, sib txawv junctions, thiab adherens junctions [65,73].
Molecules uas hla BBB los ntawm txoj kev paracellular lossis transcellular [73]. Lub physicochemical thaj chaw ntawm cov tebchaw uas tso cai rau lawv thauj thoob plaws BBB suav nrog qhov loj me, qhov hnyav molecular, kev ua haujlwm saum npoo, lipid solubility, thiab nqi [74,75].
Qee cov molecules me me (xws li ethanol, carbon dioxide, thiab barbiturates) dawb do hla BBB los ntawm kev sib kis tsis zoo [76,77].Receptor-mediated transport mechanisms suav nrog insulin transporter, transferrinreceptor, thiab glucose transporter-1 (GLUT{ {4}}) [78] kuj pab thauj cov hydrophilicmolecules xws li peptides thiab cov proteins [76].
Tsis tas li ntawd, qee lub xeev pathologic paub tias cuam tshuam qhov nruj ntawm BBB, tso cai rau cov kua dej nkag mus rau hauv lub hlwb [79–82].Thaum kawg, kev siv cov tshuaj tshwj xeeb xws li nanoparticles tuaj yeem txhim kho kev thauj khoom hla BBB. Qee qhov xwm txheej no tau tham hauv qab no.
4.2. Pharmacokinetic Cov Ntsiab Cai thiab Lawv Cov Teeb Meem ntawm Kev Xa Cov Tshuaj Hauv Lub Ncauj
Kev ua tau zoo ntawm cov tshuaj siv tshuaj feem ntau yog txiav txim siab los ntawm lawv cov tshuaj pharmacokinetic [83]. Los ntawm qhov chaw ntawm kev tswj hwm mus rau lub hom phiaj ntawm qhov chaw (qhov no, lub hlwb) yog ib qho kev taug kev nyuaj siab uas, feem ntau, tsis nyiam cov tshuaj kho.
Thawj qhov tseem ceeb ntawm kev mloog yog qhov muaj ntau yam plasma proteins uas tau muab tso rau hauv. Qee cov tshuaj muaj feem xyuam rau cov proteins no, yog li txwv cov tshuaj muaj nyob hauv kev ncig, thaum kawg txo cov tshuaj dawb muaj rau kev thauj mus los rau lub hlwb [84].
Tsis tas li ntawd, qee cov tshuaj raug tshem tawm los ntawm cov kab mob loj hauv lub cev ntawm tus nqi tseem ceeb, tsuas yog qee qhov hauv cov hlab ntsha. Tsis tas li ntawd, kev sib cuam tshuam ntawm cov tshuaj thiab lub hom phiaj lub hlwb txwv qhov kev nqus ntawm cov tshuaj.
Tshwj xeeb tshaj yog, cov tshuaj molecules tuaj yeem cuam tshuam cov hlwb ua rau kev thaiv cov kab, kev hloov pauv hauv daim nyias nyias, lossis txawm tias muaj kev hloov pauv hauv cell conformation. Qhov kev cuam tshuam ib ntus no tuaj yeem txwv tus cwj pwm ntawm lub xov tooj ntawm cov tshuaj molecule thiab nws qhov nqus tau [85]. Feem ntau, me me lipophilic tshuaj molecules tsim nyog rau lub hlwb xa [86].
5. Nanoparticles thiab lawv siv hauv NDs
Cov kev txwv uas tshwm sim los ntawm BBB thiab qhov tsis zoo ntawm cov kev kho mob tam sim no, tau hais los saum no, tau ua rau qhov tsis xav tau kev kho tshiab rau kev kho NDs [87].
Tawm ntawm txoj kev ua haujlwm, nanotechnology tau tshwm sim muaj kev nyab xeeb thiab muaj txiaj ntsig platform rau cov tshuaj / noob xa mus rau CNS [88,89].Qhov kev siv tshuab no siv cov ntaub ntawv ntawm nanoscale, feem ntau yog li ntawm 1-1000 nm, thiab tuaj yeem cuam tshuam nrog cov kab mob lom. ntawm qib molecular [90]
Muaj ntau yam ntaub ntawv xws li ntuj polymers (proteins thiab polysaccharides), hluavtaws polymers (PLGA thiab PCL), thiab inorganic cov ntaub ntawv (kub, nyiaj, thiab cerium) tau ua hauj lwm rau formulatenanoparticles.
Nanocarriers tau ua pov thawj tias yog cov tshuaj tsim nyog / cov neeg nqa mus rau lub hlwb [91]. Cov yam ntxwv ntawm nanocarriers uas ua rau lawv muaj kev cog lus platform tswj thiab kho NDs suav nrog cov tshuaj muaj peev xwm thauj khoom siab, tsis muaj tshuaj lom neeg, txhim kho tshuaj permeabilization, thiab kev ruaj ntseg ntawm lub cev thiab tshuaj lom neeg [88].
Nanoparticles nrog ntau qhov sib txawv, cov khoom, thiab kev ua haujlwm tau raug tsim los ntawm kev xa tshuaj forbrain; lawv cov ntaub ntawv muaj nyob rau hauv daim duab 2. Txawm li cas los xij, lawv qhov kev nkag mus los ntawm BBB nyob ntawm qhov loj, qhov chaw chemistry, hom, thiab polarity ntawm cov nanocarriers [92]. Tsis tas li ntawd, txheej txheej txheej nrog polysorbate tuaj yeem pab tshem tawm cov tshuab transmembraneefflux xws li P-glycoprotein twj [92].
Liposomal thiab polymeric nanoparticles tau siv ntau tshaj plaws rau lub hlwb xa khoom vim qhov yooj yim ntawm kev hloov kho nrog ligands thiab cell-peptides (CPPs) [78,93–96].
Daim duab 2. Hom nanoparticles feem ntau siv rau kev tswj cov neurodegenerativedisorders. SLN-khoom lipid nanoparticle; AuNP-gold nanoparticle, AgNP-silver nanoparticle, CeO2 NP-cerium oxide nanoparticle.
Ntawm no, peb tham txog cov nanoparticles feem ntau kawm rau kev tswj ntawm NDs.
5.1. Inorganic Nanoparticles
Hlau nanoparticles tau txais kev txaus siab ntau vim lawv muaj peev xwm hla BBB tau yooj yim thiab khaws cia hauv lub hlwb [97,98]. Lawv ntau yam khoom, xws li qhov loj me, kev hloov kho qhov chaw, thiab kev ruaj ntseg, tuaj yeem hloov kho tau yooj yim rau kev siv lub hlwb zoo [98].
Piv txwv li, cov hlau nanoparticles feem ntau ua haujlwm nrog ntau lub paj hlwb-targeted ligands, xws li cov tshuaj tiv thaiv kab mob, cov protein, thiab cov khoom me me (xws li mannose) rau kev txhim kho tshuaj xa mus rau CNS.
Cov nanoparticles no kuj paub dav rau lawv cov kev siv theragnosticand imaging applications [99,100]. Ntawm ntau yam hlau nanoparticles, kub, nyiaj, thiab cerium nanoparticles tau siv ntau tshaj plaws rau CNS tus me nyuam [97] thiab yuav tau tham txog ntawm no.
Kub nanoparticles (AuNPs) tau siv dav hauv CNS imaging thiab targeting [101]. Lawv cov tub ntxhais muaj plasmonic zog (piv txwv li, muaj peev xwm cuam tshuam nrog hluav taws xob hluav taws xob vim muaj cov hluav taws xob dawb), ua rau lawv zoo tagnrho rau kev siv duab siv micro-CT scanning lossis X-rays. Lub AuNPs yog qhov zoo tshaj hauv kev nqus thiab txo cov X-rays zoo dua li cov neeg ua haujlwm sib txawv, uas tso cai rau kev pom kev zoo dua thiab pom tseeb ntawm nanoparticles [100].
Hauv kev tshawb fawb tsis ntev los no, rhodamine Bisothiocyanate (RITC) thiab poly-L-lysine (PLL) tau complex nrog 40 nm AuNPs. Cov kev hloov kho no nce nanoparticle uptake hauv tib neeg mesenchymal qia hlwb (hMSC).
Qhov kub-labeled hMSC no tau txhaj ncaj qha rau hauv nas hlwb thiab tuaj yeem pom 30 minpost-injection siv micro-CT [102]. Ua ke nrog kev soj ntsuam ntawm tes thiab kev pom, AuNPs tau pom muaj peev xwm zoo hauv kev tsom thiab degrading -amyloid aggregates nyob rau hauv vitro mob [103]. Apolipoprotein E3 (ApoE3) conjugated nrog cov tub ntxhais ntawm AuNPs, txhawb lawv cov kev sib raug zoo nrog cov amyloid aggregates thiab nce nkag mus rau hauv lub hlwb.
Curcumin tau siv los ua kev sojntsuam los taug qab cov AuNPs. Raws li kev khi ntawm amyloid aggregates thiab ApoE3-AuNPs, qhov chaw plasmon resonance (SPR) ntawm AuNPswas tau siv los cuam tshuam cov amyloid aggregates los ntawm 60% [104]. Hauv lwm txoj kev tshawb fawb, AuNPswere nto-hloov nrog lub hlwb-targeted exosomes kom muaj txiaj ntsig zoo dua thiab txhim kho lub hlwb [105].
Sub-cellular loj, tshwj xeeb loj-raws li physicochemical thiab opticalproperties, adaptability, thiab biocompatibility ntawm AuNPs ua rau lawv haum cov cab kuj rau lub hlwb-targeted xa me me molecules thiab biomacromolecules [106].
Nyob rau hauv ib daim ntawv qhia txawv, kub nanoparticles txawv nas embryonic qia hlwb rau hauv dopaminergicneurons [107] .Silver nanoparticles (AgNPs) kuj tau tshawb nrhiav rau lub hlwb-targeted tshuaj xa.
Tom qab kev txhaj tshuaj intraperitoneal, AgNPs tau mus txog thiab tau sau tseg hauv hippocampus, uas paub tias yog thaj chaw tseem ceeb rau NDs [108]. Nws tau raug sau tseg tias 5µg / mL koob tshuaj ntawm cov nanoparticles no tuaj yeem ua rau muaj kev mob tshwm sim thiab cov kab mob neurodegenerative gene expression teb rau nas cov hlwb neural [98,109].
AgNPs tau siv los xa ntau yam tshuaj rau lub hlwb, xws li alisertib rau glioblastoma [106] mus rau cov tshuaj tiv thaiv amoebic los kho lub hlwb noj amoebae [110].
Lwm txoj kev tshawb fawb qhia txog cov tshuaj tiv thaiv kab mob thiab tshuaj tiv thaiv kab mob ntawm citrate-capped AgNPs ntawm microglia, lub hlwb lub cev tiv thaiv kab mob.Cov AgNPs no tau absorbed tshwj xeeb los ntawm microglia, uas nyob rau hauv lem coj mus rau kev qhia ntawm enzymes uas txo reactive oxygen hom thiab muaj anti-inflammatory zog [ 111] ib.
Txawm li cas los xij, qhov tsis zoo uas tau pom nrog AgNPs yog lawv cov txheej txheem nkag mus rau hauv lub hlwb, uas cuam tshuam nrog kev cuam tshuam ntawm BBB los ntawm kev ua kom tsis muaj zog ntawm kev sib tshuam.
Lawv kuj zoo li toinduce neuronal degeneration thiab necrosis los ntawm accumulating inert silver nyob rau hauv lub hlwb nyob rau hauv lub sij hawm [112–114].Cerium oxide nanoparticles feem ntau paub rau lawv lub luag hauj lwm nyob rau hauv txo oxygen hom (ROS), txuas rau neuronal tuag thiab NDs. Kev hloov pauv ntawm oxidation xeev nruab nrab ntawm Ce +3 thiab Ce +4 yog vim li cas tom qab cov tshuaj antioxidant zoo heev cov nanoparticles tso tawm [115].
Cov nanoparticles no tau ua pov thawj rau retard cov nyhuv apoptotic ntawm ADin neuronal hlwb los ntawm kev hloov lub hlwb-derived neurotrophic yam teeb liab transductionpathway thiab pom lub peev xwm txo qis A-aggregation thaum ua ke nrog PEGcoatings lossis hlau chelators [116].
Dhau li ntawm qhov no, cerium oxide nanoparticles tau txais txiaj ntsig zoo peroxynitrite ROS hauv cov qauv ischemic stroke thiab rov ua haujlwm ntawm lub cev muaj zog hauv ntau-sclerosis- thiab ALS-nas qauv [117].
Tsis ntev los no, ob peb nanoparticle-based formulations tau sau tseg nrog neurogenesis muaj peev xwm. Zavvari li al., 2020 tshawb nrhiav cov txiaj ntsig neurogenesis ntawm cerium dioxide (CeO2) nanoparticles.
Lawv tau thov tias kev tswj hwm ib zaug ntawm CeO2 nanoparticles txaus los pib neurogenesis hauv thaj av hippocampal. Qhov no yog vim muaj kev tiv thaiv kab mob thiab neuro-regenerativepotency ntawm cerium oxide [118].
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