Quercetin Attenuates Neurotoxicity Induced Los ntawm Hlau Oxide Nanoparticles Part 1

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Keeb kwm

Lub sij hawm nanomaterial yog hais txog cov khoom nyob rau hauv nanoscale (1-100 nm) nrog ib, ob, los yog peb sab nraud qhov ntev, whereas lub sij hawm nanoparticle (NP) hais txog cov ntaub ntawv nrog tag nrho peb sab nraud qhov ntev hauv nanoscale [1]. Cov khoom tseem ceeb tshaj plaws ntawm NPs yog qhov siab tshaj plaws rau huab hwm coj piv, kev ua haujlwm catalytic, hluav taws xob thiab thermal conductivity, siab solubility, thiab kev txav mus los hauv lub cev [2]. Muaj ob pawg dav dav ntawm biomedicine NPs. (I) Organic NPs yog tsim los ntawm cov organic molecules. Liposomes, emulsions, dendrimers, thiab lwm yam polymers tsim ib pawg loj ntawm cov organic NPs.(II) Inorganic NPs uas muaj cov hlau tseem ceeb xws li hlau, npib tsib xee, cobalt, kub, silica, thiab hlau oxides nrog hluav taws xob, sib nqus, kho qhov muag, thiab fluorescent zog [3]. Iron oxide nanoparticles (IONPs) yog ib chav kawm ntawm cov hlau nplaum nanoparticles (MNPs) uas tau txais qhov tseem ceeb hauv kev nce qib hauv kev siv tshuab [4,5].IONPs feem ntau yog ua) core thiab magnetite (FeO) lossis maghemite (y-Fe, O3) a tiv thaiv txheej xws li chitosan, dextran, polyethylene glycol (PEG), thiab polyvinyl cawv (PVA) [6-8]. IONPs muaj cov khoom tshwj xeeb uas ua rau lawv tsim nyog biomaterials rau kev siv kho mob. Piv txwv li, lawv tus cwj pwm Ferro-lossis ferromagnetic ua rau muaj kev lag luam tshuaj thiab kev qhia tshuaj rau cov ntaub so ntswg. Lawv tuaj yeem nyob hauv cov ntaub so ntswg tshwj xeeb nyob rau hauv ib qho chaw sib nqus sab nraud kom lawv hu ua magnetic targeted carriers (MTC)[9]. Ntxiv mus, daim ntawv thov ntawm IONPs hauv magnetic resonance imaging (MRI) yog ib qho cuab yeej muaj zog rau kev tsim cov duab kho mob siab zoo thiab txhim kho lub peev xwm ntawm kev kuaj mob [6,10].

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Thov nias ntawm no kom paub ntxiv

Tsis tas li ntawd, IONPs tuaj yeem ua rau cov qog nqaij hlav cancer ntau dua rau hluav taws xob thiab tshuaj khomob los ntawm qhov kub thiab txias (hyperthermia). Tsis tas li ntawd, lub peev xwm ntawm IONPs hla cov ntshav-hlwb barrier (BBB) yog ib qho khoom muaj cai rau kev thauj cov tshuaj mus rau lub hlwb hauv cov kab mob neurological [6-8]. Tam sim no, muaj ntau yam FDA pom zoo SPION cov tebchaw (xws li, ferumoxide (Feridex IV), ferumoxytol (Lumirem), thiab ferumoxytol (Feraheme)), rau kev siv hauv tsev kho mob thiab lwm yam kev sim tshuaj, nrog rau cov lej ntawm IONPs. , ua tsis tu ncua. Txawm hais tias cov txiaj ntsig tau hais los saum no, hauv vitro, thiab hauv vivo cov kev tshawb fawb tau muab pov thawj hais txog qhov muaj peev xwm neurotoxicity ntawm IONPs vim yog dawb hlau tsub zuj zuj, ROS ntau lawm, thiab protein aggregation [11-14]. Txawm li cas los xij, kev hloov kho cov khoom siv physicochemical ntawm NPS xws li concentration, qhov loj me, thiab txheej txheej tuaj yeem ua kom zoo dua lawv txoj haujlwm thiab cytotoxicity zog [14]. Tsis tas li ntawd, kev siv tib lub sijhawm ntawm cov tshuaj antioxidants xws li quercetin (QC) supplementation tuaj yeem yog txoj hauv kev zoo los tshem tawm cov hlwb oxidative puas tsuaj vim IONPs [15]. QC(3,3',4',5,7-pentahydroxy flavone) belongs rau cov chav kawm flavonoid thiab flavonol subclass nrog cov tshuaj formula C15H10O7[16]. QC yog cov khoom tseem ceeb hauv ntau cov txiv hmab txiv ntoo, noob, zaub, thiab txiv ntoo. Cov txiaj ntsig zoo ntawm QC tau tshawb xyuas ntau yam mob xws li mob qog noj ntshav thiab kab mob neurodegenerative [17, 18]. QC tuaj yeem ncua lossis tiv thaiv kab mob neurodegenerative los ntawm ntau txoj hauv kev molecular [16, 19]. QC modulates oxidative kev nyuaj siab ntawm kev khi rau cov pa reactive oxygen thiab / los yog nitrogen hom (ROS / RNS) thiab los ntawm nws cov nyhuv ntawm kev qhia thiab kev ua ntawm enzymatic / non-enzymatic antioxidants [15, 20]. QC tseem tiv thaiv Fenton cov tshuaj tiv thaiv los ntawm kev tsim cov hlau ruaj khov-QC complexes, yog li tshem tawm ROS / RNS [18] ncaj qha. Ntxiv mus, nyob rau hauv hlau overload tej yam kev mob QC, yuav tswj hlau homeostasis [21]. QC tsis tuaj yeem hla BBB zoo vim nws qhov kev solubility tsawg, tsis ruaj khov, thiab tsis muaj bioavailability [20]. Kev siv IONPs yog ib qho kev daws teeb meem zoo los kov yeej cov kev txwv no [22]. Yog li ntawd, kev sib koom ua ke QC nrog IONPs yog ib qho kev sib koom ua ke los ua kom tsis muaj zog hlau toxicity thiab nce QC bioavailability. Cov txiaj ntsig zoo ntawm QC tawm tsam IONPs-induced neurotoxicity yog txhais tsis zoo. Hauv kev tshuaj xyuas no, peb muab pov thawj tias QC tuaj yeem tiv thaiv cov hlau overload-induced toxicity. Qhov no hlau overload tuaj yeem tshwm sim los ntawm IONPs metabolism lossis lwm qhov chaw. Txawm li cas los xij, QC yuav muaj cov dej num sib npaug rau kev tshem tawm cov hlau ntau dhau los ntawm ntau qhov chaw.

Cistanche tuaj yeem tiv thaiv Alzheimer's kab mob

Hlau metabolism thiab homeostasis

Hlau nyob rau hauv peb lub cev yog ib qho tseem ceeb mineral rau ntau yam txheej txheem xws li oxygen thauj thiab mitochondrial muaj nuj nqi. Hlau, kuj yog ib qho kev sib koom ua ke, koom nrog cov tshuaj tiv thaiv enzymatic xws li, DNA replication, RNA transcription, protein translation, thiab myelin synthesis [23,24]. Tib neeg lub cev muaj li ntawm 3-4 g ntawm hlau uas tej zaum yuav poob mus txog rau 0.1 feem pua txhua hnub nyob rau hauv physiological thiab pathological tej yam kev mob uas feem ntau yog compensated nrog kev noj haus txhua hnub [25]. Ob qho tib si tsis muaj hlau thiab hlau ntau dhau tuaj yeem cuam tshuam rau kev loj hlob thiab kev ua haujlwm ntawm lub hlwb los ntawm fetal mus rau cov neeg laus [26-28]. Muaj ob hom hlau nyob rau hauv cov khoom noj txhua hnub: heme hlau nrog absorbable ferrous ion (Fe2) uas muaj nyob rau hauv cov nqaij liab thiab nqaij nruab deg, thiab tsis-heme hlau nrog ferric ion (Fe3 ntxiv) uas muaj nyob rau hauv cov zaub mov raws li cog [29,30 ]. Kev nqus hlau tuaj yeem tswj tau los ntawm cov qib hlau hauv lub cev thiab ntau tus neeg saib xyuas hlau [27]. Duodenal cytochrome B (Dcytb) yog ib qho ascorbate-dependant plasma transmembrane ferrireductase uas hloov Fe3 ntxiv rau Fe2 ntxiv rau ntawm daim nyias nyias ntawm lub plab zom mov, enterocytes [31]. Hlau nkag mus rau hauv lub cell los ntawm cov hlau thauj mus los [32] Divalent hlau transporter 1 (DMT1) thiab heme carrier protein 1 (HCP1) yog lub ntsiab tsis-heme thiab heme hlau thauj khoom, feem. Lawv tuaj yeem hloov Fe2 ntxiv thiab heme los ntawm lub plab lumen mus rau hauv enterocytes [29,30,32]. HCP1 yog qhov zoo dua yog qhov kev sib raug zoo siab ntawm folate transporter [33]. Nyob rau hauv cov kauj ruam tom ntej, Fe2 ntxiv tshwm sim los ntawm non-heme thiab heme hlau degraded los ntawm heme oxygenase-1(HO-1) nkag mus rau lub labile hlau pas dej (LIP), ib tug transient intracellular hlau pas dej ua ke[23]. Feem ntau ntawm no Fe2 ntxiv yog tso tawm los ntawm lub cell los ntawm hlau exporter ferroportin nyob rau hauv lub basolateral membrane ntawm enterocytes [34]. Nws cov nyiaj seem yog pauv mus rau cytosolic hlau-cia protein hu ua ferritin. plab hnyuv ferritin yog qhov ua tau zoo hauv kev nqus hlau vim yog ferroxidase kev ua haujlwm ntawm nws cov H subunit uas rov oxidizes Fe2 ntxiv rau Fe3 ntxiv [23,35,36].Ntawm qhov tod tes, cov hlau tso tawm los ntawm cov enterocytes yog re-oxidized rau. Fe3 ntxiv los ntawm ferroxidases (ie., membrane-bound multicopper hephaestin thiab soluble thiab/membrane-bound multicopper ceruloplasmin), uas koom nrog hauv cov hlau xa tawm los ntawm ferroportin [37, 38]. Hlau oxidation yog qhov tseem ceeb rau kev hloov hlau los ntawm plasma iron-free transferrin, thiaj li hu ua apo-transferrin (Apo-Tf). Traping thiab khaws Fe3 ntxiv los ntawm cov hlau khaws cov proteins xws li ferritin thiab transferrin suppresses Fe3 ntxiv rau reactivity thiab dawb radical tiam [39]. Apo-Tf khi rau ob lub ferric ions ntawm ib txwm alkaline pH (7.4) ntawm plasma los ua holo-transferrin (Holo-Tf). Qhov no hlau-loaded glycoprotein raws li ib tug plasma hlau pas muab hlau mus rau lub hom phiaj cov ntaub so ntswg xws li pob txha pob txha, daim siab, thiab hlwb [25,40, 41](Fig.1). Hepatocytes thiab macrophages yog lub luag haujlwm rau kev khaws cov hlau thiab cov hlau rov ua dua tshiab, feem [42]. Nyob rau hauv physiological mob, kwv yees tag nrho

ntawm cov hlau extracellular nkag mus rau lub hom phiaj ntawm tes nyob rau hauv daim ntawv ntawm transferrin-bound. Txawm li cas los xij, transferrin saturation vim hlau overload tiv thaiv hlau binding rau transferrin thiab ua rau non-transferrin bound hlau (NTBI) uptake [43]. Holo-Tf khi rau transferrin receptor (TfR) nyob rau saum npoo ntawm cov hlwb feem ntau [44]. Holo-Tf-TfR complex yog nyob rau hauv lub cell ntawm clathrin-coated vesicles nrog rau adapter protein 2 (AP2) nyob rau hauv lub endocytosis voj voog hu ua clathrin-mediated endocytosis (CME) [45,46]. Lub endocytic vesicles poob lawv cov clathrin txheej thiab tom qab ntawd merged rau hauv endosome membrane[45, 47]. Fe ntxiv nyob rau hauv acidic pH (5.{16}}.0) ntawm lig endosome yog tso tawm los ntawm ib tug Transferrin-TR complex thaum, transferrin tseem khi rau TfR thiab reconverted rau Apo-Tf. Tsis tas li ntawd, endo-somal ferrireductase xws li 6-transmembrane epithelial antigen ntawm prostate (Step) txo cov insoluble Fe3 ntxiv rau soluble Fe2 ntxiv rau qhov uas yog thauj los ntawm endosomal lumen mus rau hauv cytosol los ntawm DMT1.Apo-Tf khi rau TfR. yog recycled rau lub cell nto thiab dissociates los ntawm lub receptor ntawm pH ntawm 7.4 [38,{29}}]. Ntawm no, TfR npaj txhij los khi Holo-Tf tom ntej thiab pib rov ua dua tshiab [51]. Cytosolic hlau confronts ob peb txoj kev: (I) kev koom tes nyob rau hauv lom functions los ntawm embedding nyob rau hauv metalloproteins, (I) kev koom tes nyob rau hauv mitochondrial zog transduction, (II) cia nyob rau hauv daim ntawv ntawm ferritin [48,52]. Tsis tas li ntawd, lysosomal degradation ntawm ferritin ua rau tsim cov hlau khaws cia complex, uas yog, haemosiderin, uas muaj feem xyuam rau cov xeev pathophysiological (piv txwv li, hlau overload) thiab koom nrog hauv ib qho reactive dawb radical tiam [30,48].

immunity2

Iron homeostasis yog tswj hwm los ntawm ntau yam xws li hepcidin hormone thiab cov protein tswj cov hlau (IRP1 thiab IRP2) / hlau teb cov ntsiab lus (IRE) qhia txoj hauv kev [42]. Hepcidin, uas yog tsim los ntawm lub siab, yog ib qho tseem ceeb ntawm kev tswj hwm. Thaum muaj hlau ntau, hepcidin khi rau enterocyte ferroportin thiab thaiv cov hlau xa tawm ntawm tes [35,42]. Ntawm qib cellular, IRP / IRE signaling txoj kev tswj cov hlau homeostasis nyob ntawm lub cev cov hlau ntau. Hauv kev tsis muaj hlau tsis muaj hlau, IRP khi rau IRE motif ntawm thaj tsam 5'-untranslated (5'UTR) ntawm ferroportin thiab ferritin cov ntawv sau tseg kom txwv tsis pub txhais ntawm lawv cov mRNAs. Txawm li cas los xij, kev khi ntawm IRPs rau IRE motif ntawm 3'-UTR tawm thiab DMT1 cov ntawv sau cia ruaj khov rau lawv cov mRNAs txhawm rau txhim kho kev txhais lus. Cov txheej txheem no ua rau txo cov ntshav plasma hlau thiab nce cellular hlau siv rau hauv cov txheej txheem metabolic [50]. Ntawm qhov tsis sib xws, thaum cov hlau muaj ntau, IRP tsis tuaj yeem khi rau IRE motif ntawm 5'UTR ntawm ob qho tib si ferroportin thiab ferritin transcripts thiab txhim kho kev txhais lus ntawm lawv mRNAs thiab IRP tsis tuaj yeem khi rau IRE motif ntawm 3'-UTR ntawm TfR. thiab DMT1 transcripts thiab destabilizes mRNAs los txwv kev txhais lus [53].

Hlau hauv hlwb

Vim yog qhov tseem ceeb ntawm cov kab mob neurodegenerative thiab txawv txav ntawm cov hlau metabolism, cov lus piav qhia meej ntawm txoj hmoo ntawm cov hlau hauv CNS yog qhov tsim nyog [48]. Hlau hauv CNS ua lub luag haujlwm tseem ceeb hauv ntau lub cev tsis muaj zog, suav nrog kev faib tawm ntawm tes, kev tsim hluav taws xob, axons myelination, dendritic branching, thiab neurotransmitters synthesis xws li dopamine thiab serotonin [24, 53-55]. Hlau yog qhov sib koom ua ke rau tyrosine hydroxylase uas koom nrog hauv dopamine synthesis thiab tryptophan hydroxylase uas koom nrog hauv serotonin syn-thesis [54]. Dopamine yog ib hom catecholamine nyob rau hauv lub hlwb uas tuaj yeem tso tawm rau qee qhov chaw ntawm hippocampus, tej zaum yog thaj tsam CL, thiab txhim kho lub sijhawm ntev (LTP) [56]. Hlau deficiency yog txuam nrog txo myelin synthesis, uas yog tsim los ntawm myelinating glial hlwb xws li, oligodendrocytes, ua raws li los ntawm qhov tshwm sim xws li kev puas hlwb [57]. Hlau yog thauj mus rau hlwb hlwb los ntawm cov ntshav-hlwb barrier (BBB) thiab cov ntshav-CSF barrier (BCB). Feem ntau ntawm cov hlau nkag mus rau hauv lub hlwb interstitial kua (ISF) los ntawm hla BBB, thiab qee cov hlau nkag mus rau hauv cov kua cerebrospinal (CSF) los ntawm hla BCB hauv choroid plexus [58]. Txoj kev Holo-Tf-TfR yog ib txoj hauv kev paub zoo ntawm cov hlau mus rau lub hlwb [59]. Zoo li lwm hom cell uas tau hais los saum no, ncig Holo-Tf khi rau TfR ntawm daim nyias nyias ntawm capillary endothelial hlwb ntawm BBB thiab choroid plexus epithelial hlwb ntawm BCB. Qhov kev khi no tau ua rau cov cell membrane budding nrog rau Holo-Tf-TfR complex los ntawm CME txheej txheem. Daim ntawv txo cov hlau tuaj yeem xa tawm los ntawm lub hlwb capillary los ntawm ferroportin mus rau ISF thiab CSF tom qab dissociation los ntawm nws. Tom qab rov oxidizing ntawm Fe2 ntxiv rau Fe3 kho los ntawm ferroxidases, Fe3 ntxiv khi rau transferrin thiab uptakes los ntawm neural hlwb (xws li, oligo-dendrocytes, astrocytes, microglia, thiab neurons) ntawm receptor-mediated endocytosis [23,24,58, 60-62]. Txawm li cas los xij, qee cov hlau tuaj yeem ua rau hauv daim ntawv ntawm NTBI, yuav yog DMT1 [59] tom qab txo Fe3 ntxiv rau Fe2 ntxiv los ntawm ferri-reductase [63](Fig.2). Iron uptake los ntawm neurons suav nrog kev hloov pauv cov hlau thiab NTBI. Upregulation ntawm TfR ntawm neurons nyob rau hauv cov hlau tsis muaj peev xwm, tawm tswv yim nws kim heev transferrin-bound hlau uptake los ntawm no receptor [64]. Neurons thiab lwm hom cell yuav tau txais NTBI los ntawm DMT1. Txawm li cas los xij, cov txheej txheem ntawm NTBIuptake tsis tau qhia meej meej [65]. Hlau exporter nyob rau hauv neurons yog tib yam li ferroportin uas tau nthuav tawm thoob plaws lub cell membrane. Ferritin raws li ib qho khoom noj khoom haus hlau kuj tau pom nyob rau hauv qee cov neurons [64] (xws li, dopaminergic neurons) [66]. Hlau kuj tseem muaj nyob rau hauv qhov chaw synaptic ntawm neurons, uas tau tso tawm los ntawm axon terminus [24]. Muaj ob peb lub tswv yim rau cov hlau rov ua dua tshiab rau cov kab ke hauv lub cev. Piv txwv li, Holo-Tf khi rau TfR ntawm abluminal membrane ntawm BBB, thiab arachnoid granulations-mediated tsheb thauj mus los tau raug npaj los ua ib lub tswv yim los xa cov hlau los ntawm lub hlwb mus rau hauv [67]. Cov hlau ntau dhau los ntawm cov kab mob pathological lossis senescence kuj rov qab mus rau lub cev. Moos li al., los ntawm kev txhaj tshuaj ntawm transferrin radiolabeled nrog 5Fe thiab 12I mus rau hauv lub ventricles lateral, npaj ib txoj kev loj ntawm hlau reabsorption mus rau hauv cov ntshav plasma uas yog tshwm sim los ntawm subarachnoid thiab thauj los ntawm BCB [68]. Tsis tas li ntawd, kev tshem tawm ntawm cerebral apoptotic / necrotic hlwb nyob rau hauv cov mob inflammatory ntawm phagocytosis txhawb nqa cov hlau mus rau hauv cov ntshav ntshav los ntawm lub hlwb los ntawm phagocytes [64]. Txawm li cas los xij, qhov tseeb mechanism ntawm hlau xa rov qab mus rau lub cev tsis meej thiab xav tau kev tshawb fawb ntxiv.

Hlau overload-induced neurotoxicity

Hlau yog cov khoom siv tshuaj uas muaj nyob rau hauv cov hlau hloov pauv nrog cov khoom siv hluav taws xob thiab kev lees paub [69]. Txawm hais tias hlau yog ib qho tseem ceeb hauv kev ua haujlwm neuro, nws qhov ntau dhau tuaj yeem ua rau cov protein sib sau ua ke thiab oxidative kev nyuaj siab. Nws cov txiaj ntsig zoo tshaj plaws yog kev tuag ntawm cov hlwb neuronal [14, 70]. Yog li ntawd, txoj cai raug cai ntawm cov hlau homeostasis yuav tsum tau [69]. Cov hlau tsub zuj zuj zuj zus feem ntau tshwm sim hauv kev laus ib txwm muaj tab sis ntau lub hnub nyoog-nyob ntawm / ywj pheej muaj feem cuam tshuam nrog nws txoj kev loj hlob suav nrog kev haus luam yeeb, qhov siab ntawm lub cev qhov ntsuas (BMI) [70], kev hloov pauv ntawm cov hlau ntau dhau (xws li hemochromatosis) [71], kev hloov pauv ntawm cov hlau. overload nyob rau hauv hom anemia [72], thiab cov kab mob neurodegenerative [73]. Tsis tas li ntawd, kev siv IONPs hauv kev kuaj mob thiab kho cov kab mob (xws li kab mob neurodegenerative) tuaj yeem ua rau cov hlau accu-mulation[14, 15]. Cov hlau ntau dhau yog ib qho tseem ceeb hauv cov kev cuam tshuam uas ua rau cov ntaub so ntswg puas los ntawm kev tsim tawm ntau dhau ROS / RNS, uas yog luv luv hu ua RONS [74, 75]. Qhov xwm txheej no ua rau muaj qhov tsis sib xws ntawm antioxidants thiab prooxidants, uas yog hu ua nitrosative thiab / lossis oxidative stress [74]. Txawm hais tias kev sib raug zoo ntawm cov hlau overload thiab nitrosative kev nyuaj siab, nws tsis txaus piav qhia. Yog li ntawd, nyob rau hauv txoj kev tshawb no, peb tsom rau kev sib raug zoo ntawm hlau overload thiab oxidative kev nyuaj siab. Lub hlwb yog lub cev rhiab heev rau ROS vim kev noj cov pa thiab hlau tsis tu ncua, muaj feem pua ntawm cov roj ntsha polyunsaturated fatty acids (PUFAs) uas muaj qhov tsis zoo rau oxidation, thiab kev tiv thaiv antioxidant tsis muaj zog hauv kev sib piv nrog lwm cov ntaub so ntswg [76]. Raws li lub cev muaj zog, ROS yog tsim los ntawm cov cellular metabolism. Oxygen (O) txo ntawm Fe2 ntxiv ua rau Fe3 thiab superoxide anion (O,.) uas yog ib qho ua ntej ntawm lwm hom reactive (2Fe2 ntxiv rau 2O, → 2Fe ntxiv rau 2O,). Superoxide dismutase (SOD) enzyme converts O. rau hydrogen peroxide (H2O) thiab O2 (2O2…- ntxiv 2H ntxiv rau → H, O2 ntxiv rau O2). H, O2 hloov mus rau dej (H2O) ntawm cov enzymes antioxidant xws li glutathione peroxidase (GPX) thiab catalase (CAT) (2H, O, → 2H, O ntxiv rau O). Cov tshuaj tiv thaiv no tau ua tib zoo tswj thiab suav tias yog ib feem ntawm lub xov tooj ntawm tes taw qhia [77, 78]. Txawm li cas los xij, H, O2 nkag mus rau kev puas tsuaj Fenton cov tshuaj tiv thaiv nyob rau hauv lub xub ntiag ntawm redox-active bio hlau xws li dawb hlau. Thaum lub sij hawm Fenton cov tshuaj tiv thaiv, Fe2 ntxiv raws li ib tug electron pub

Cov hluav taws xob rau H, O, txo qis li Fe3, hydroxide (HO-), thiab tsis muaj zog hydroxyl radical (OH') yog tsim (HO, ntxiv Fe2 ntxiv rau → Fe3 ntxiv rau OH- ntxiv OH'). txo ntawm O.- hauv cov hlau- Ntawm qhov tod tes, Fe3 ntxiv rau r sulfur proteins, txuas ntxiv Fe2 ntxiv rau Fenton cov tshuaj tiv thaiv (Fe3 ntxiv rau O.- → Fe2 ntxiv rau O,) [77,78]. Raws li, cov tshuaj tiv thaiv raug xa mus rau Haber-Weiss cov tshuaj tiv thaiv uas yuav tsum tau muaj cov hlau ions (O·- ntxiv rau H, O, → OH" ntxiv rau O2 ntxiv rau OH-)[23].Iron overload thiab ROS sib koom ua ke thiab ua rau cov nucleic acids puas tsuaj. , lipids, proteins, thiab cellular compartments xws li mitochondria [24].ROS tshwm sim los ntawm Fenton cov tshuaj tiv thaiv tuaj yeem ua rau oxidation ntawm DNA bases. Cov kab mob no tau kho los ntawm cov txheej txheem tseem ceeb ntawm DNA kho hu ua base excision repair (BER). Nyob rau hauv cov xwm txheej hlau overload, hlau ncaj qha khi rau ob BER enzymes nrog rau nei zoo li DNA glycosylase (NEIL1) thiab NEIL2 yog li inhibiting lawv enzymatic kev ua si [79]. , ROS ncaj qha cuam tshuam nrog daim nyias nyias PUFAs los tsim cov tshuaj lom aldehydes xws li 4-Hydroxynonenal (4-HNE) thiab Malondialdehyde (MDA). Hlau yog ib qho accelerator rau cov txheej txheem no. Tsis tas li ntawd, ROS los ntawm kev tawm tsam membrane proteins ua rau kev hloov pauv nyob rau hauv architecture, permeability, rigidity, thiab kev ncaj ncees ntawm daim nyias nyias [76]. Cov khoom lag luam lipid peroxidation tuaj yeem tsim cov protein tsis zoo ntawm carbonylation. Lub ubiquitin-proteasome system tsis tuaj yeem degrade misfolded proteins yog li protein aggregation thiab neurodegeneration tuaj yeem tshwm sim [14]. Lub mitochondrial daim nyias nyias yog qhov ua rau puas vim muaj qib siab ntawm PUFAs [80]. Tshaj hlau-induced ROS nce mitochondrial membrane permeability, uas tso tawm hlau los ntawm cov organelle. Tsis tas li ntawd, cov hlau ntau dhau cuam tshuam rau kev sib koom tes ntawm cov hlau thiab calcium uas yog qhov kev taw qhia hauv qab ntawm txoj hauv kev uas muaj feem xyuam nrog kev paub txog kev txawj ntse xws li synaptic plasticity, mitochondrial function, thiab axon kev loj hlob tuaj yeem raug rhuav tshem.

3 (1)

Ntau cov hlau tsis tsuas yog ua rau mitochondrial tsis ua haujlwm tab sis kuj ua rau kev tso tawm calcium thiab cytochrome C los ntawm cov kab mob no mus rau cytosol thiab thaum kawg ntawm tes tuag [14,81]. Dopamine-induced neurotoxicity kuj tau tshaj tawm tias yog lwm lub tshuab ntawm hlau-dependent neurodegeneration. Hauv qhov no, metabolites uas tshwm sim los ntawm ntau dhau oxidation ntawm dopamine (xws li, reactive quinones) ua rau neuronal tuag. Cov txheej txheem no yog nrawm los ntawm ntau cov hlau thiab oxidative kev nyuaj siab [82]. Nyob rau hauv physiological tej yam kev mob, neurons tshem tawm oxidation khoom los ntawm ob peb mechanisms. Piv txwv li, glutathione (GSH) yog ib qho muaj zog antioxidant uas sib npaug hauv cov cellular oxidants los ntawm kev khi rau cov khoom oxidation thiab tshem tawm ntawm cov neurons [76, 82]. Txawm li cas los xij, nyob rau hauv pathological tej yam kev mob, hlau overload txo cov theem ntawm GSH uas ua rau TfR overexpression thiab re-induction ntawm oxidative kev nyuaj siab.Ib theem siab ntawm TfR ua rau ntau hlau influx mus rau hauv lub cell uas exacerbates hlau overload thiab oxidative kev nyuaj siab [14]. Yog li ntawd, hlau overload nrog cov khoom oxidation thawj xws li OH, lwm yam oxidation khoom xws li tshuaj lom aldehydes, thiab protein aggregation yuav induce neuronal cell tuag [76]. Ferroptosis yog ib qho kev tuag ntawm cov hlau uas cuam tshuam nrog cov kab mob degenerative thiab non-degenerative xws li Alzheimer's disease (AD), Parkinson's dis-ease (PD), thiab mob stroke [81]. Ferroptosis txawv ntawm hom programmed thiab non-programmed cell tuag.Nws yog qhov kawg ntawm oxidative kev nyuaj siab thiab lipid peroxidation (Fig.3). Thaum lub sijhawm ferroptosis txo qis hauv GSH qib thiab GPX kev ua haujlwm ua rau lipid peroxidation nyob rau hauv muaj Fe2 [83]. Ferroptosis yog tiv thaiv los ntawm antioxidants uas koom nrog hauv cov hlau chelation thiab tiv thaiv lipid peroxidation kev ua haujlwm [81]. Cov ntsiab lus siab ntawm cov hlau tau pom nyob rau hauv ntau qhov chaw ntawm lub hlwb nrog rau lub paj hlwb cortex, hippocampus, cerebellum, amygdala, thiab basal ganglia, nyob rau hauv cov neeg laus noj qab nyob zoo, uas cov cheeb tsam no feem ntau yuav koom nrog cov kab mob neurodegenerative. Hlau concentration nyob rau hauv lub hlwb ntawm cov neeg mob nrog neurodegeneration yog notably siab tshaj nyob rau hauv noj qab haus huv laus [24] .Iron overload nyob rau hauv kev laus tuaj yeem tshwm sim los ntawm ntau txoj hauv kev xws li mob, ua rau BBB permeability, thiab cuam tshuam hauv cov hlau homeostasis. Tsis tas li ntawd, hlau overload nyob rau hauv neuroglia thiab neurons aggravates neuroinflammation thiab ua rau neuronal apoptosis [24]. Muaj kev sib raug zoo ntawm cov hlau tsub zuj zuj, lub hlwb kev laus, thiab cov kab mob neurological xws li AD[84], PD[85], thiab mob stroke [86](Fig.4).

Kab lus no yog muab rho tawm los ntawm Bardestani li al. J Nanobiotechnol (2021) 19:327 https://doi.org/10.1186/s12951-021-01059-0