Crosstalk Ntawm Neuron Thiab Glial Cells hauv Oxidative Injury Thiab Neuroprotection Part 1
Mar 22, 2024
Abstract:
Txhawm rau tiv thaiv oxidative kev nyuaj siab thiab cov kab mob hauv lub hlwb, cov kab mob antioxidant cawm cov hlwb ntawm oxidative kev nyuaj siab los ntawm kev ua kom cov pa oxygen reactive thiab khaws cia cov noob caj noob ces.
Kev sib raug zoo ntawm antioxidant kev nyuaj siab thiab kev nco yog lub ntsiab lus ntawm kev txhawj xeeb loj. Nyob rau hauv lub neej niaj hnub no, kev ntxhov siab thiab kev ua qias tuaj ib puag ncig peb ntsib ua rau muaj kev puas tsuaj ntawm cov dawb radicals thiab oxidative kev nyuaj siab, uas tuaj yeem cuam tshuam rau peb lub cev, nrog rau kev puas tsuaj rau peb lub hlwb thiab kev nco.
Txawm li cas los xij, peb tsis tas yuav txhawj xeeb txog cov teeb meem no. Cov kws tshawb fawb tau ua pov thawj tias los ntawm kev muab cov tshuaj antioxidants tsim nyog, nws muaj peev xwm txo qis kev tsim cov dawb radicals thiab tiv thaiv oxidative kev nyuaj siab. Qhov no muab peb txoj hauv kev yooj yim tab sis siv tau los txhim kho peb lub cim xeeb.
Ntau yam antioxidants tau pom tias tiv thaiv hlwb hlwb los ntawm kev puas tsuaj los ntawm oxidative kev nyuaj siab. Cov tshuaj antioxidants no suav nrog vitamin E, vitamin C, carotenoids, selenium, thiab lwm yam. Cov kws tshawb fawb ntseeg tias thaum peb lub cev raug dej nyab nrog cov antioxidants, peb lub hlwb muaj kev tiv thaiv ntau dua los ntawm kev tawm tsam dawb radicals thiab oxidative kev nyuaj siab.
Tsis tas li ntawd, kev tawm dag zog me ntsis kuj tuaj yeem pab peb tua cov dawb radicals thiab oxidative kev nyuaj siab. Kev tawm dag zog tsis tu ncua txhim kho cov pa oxygen, ua kom cov ntshav khiav, thiab ua kom lub cev muaj peev xwm tsim cov tshuaj antioxidants. Cov txheej txheem no thaum kawg pab peb txhim kho peb lub cim xeeb, ua rau peb tsom ntsoov ntau dua thiab muaj peev xwm nco tau tej yam zoo dua.
Thaum kawg, nyob rau hauv lub neej txhua hnub, peb cov khoom noj yuav tsum tau them sai sai rau kev sib xyaw ua ke. Peb yuav tsum xyuas kom meej tias peb noj cov vitamins, minerals, thiab fiber ntau hauv peb cov pluas noj, uas pab peb tiv thaiv dawb radicals thiab oxidative kev nyuaj siab. Nyob rau tib lub sijhawm, peb yuav tsum tsis txhob noj cov zaub mov uas muaj roj ntau thiab qab zib ntau dhau kom tsis txhob tsim cov tshuaj phem ntau dua.
Nyob rau hauv luv luv, kev sib raug zoo ntawm antioxidant kev nyuaj siab thiab nco yog inseparable. Peb tuaj yeem tiv thaiv peb lub hlwb los ntawm kev puas tsuaj ntawm oxidative kev nyuaj siab thiab tsim kom muaj kev paub zoo dua los ntawm kev txhim kho peb lub cim xeeb los ntawm kev noj zaub mov kom raug, kev tawm dag zog, thiab tshuaj ntxiv. Yog li cia peb pib txij tam sim no mus thiab ua kom muaj zog tiv thaiv peb lub cev thiab kev nco, thiab ua lub neej muaj zog thiab muaj zog! Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco zoo vim Cistanche deserticola yog cov khoom siv tshuaj hauv Suav teb uas muaj ntau yam teebmeem, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm Cistanche deserticola los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog tannic acid, polysaccharides, flavonoid glycosides, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.
Nyem paub 10 txoj hauv kev los txhim kho kev nco
Nws yog ib qho tsim nyog kom nkag siab txog kev sib txuas lus thiab kev sib cuam tshuam ntawm cov hlwb hlwb, suav nrog cov neurons, astrocytes, thiab microglia, kom nkag siab txog oxidative kev nyuaj siab thiab cov txheej txheem antioxidant.
Ntawm no, lub luag haujlwm ntawm glia hauv kev tiv thaiv cov neurons tiv thaiv kev raug mob oxidative thiab glia-neuroncrosstalk los tswj cov tshuaj tiv thaiv antioxidant thiab tiv thaiv lub hlwb.
Thawj feem ntawm qhov kev tshuaj xyuas no tsom mus rau lub luag haujlwm ntawm glia hauv kev hloov pauv morphological thiab physiological xav tau rau lub hlwb homeostasis nyob rau hauv oxidative kev nyuaj siab thiab antioxidant tiv thaiv mechanisms. Qhov thib ob tsom rau qhov tseem ceeb crosstalk ntawm neurons thiab glia rau redox tshuav nyiaj li cas hauv lub hlwb tiv thaiv kev ntxhov siab oxidative.
Ntsiab lus: neuron-glia kev sib cuam tshuam; astrocyte; microglia; oxidative kev raug mob; neurotiv thaiv.
1. Taw qhia
Lub paj hlwb muaj kev cuam tshuam rau oxidative raug mob vim nws qhov siab ntawm oxidativemetabolic kev ua si, khaus ntau lawm ntawm reactive oxygen metabolites, tsis muaj zog antioxidant capacity, kuj siab lipid cov ntsiab lus, siab zog yuav tsum, tsis-replicating neuronalcells, thiab siab membrane nto-to-cytoplasm piv. .
Yog li ntawd, oxidative raug mob induces neurodegenerative kab mob [1,2]. Tshwj xeeb tshaj yog, reactive oxygen hom (ROS) ua rau muaj kev cuam tshuam rau lub hlwb kev puas tsuaj thiab kev ua haujlwm tsis zoo ntawm redox imbalance ntawm pro-oxidant thiab antioxidant agents, uas induce tsim cov dawb radicals thiab lwm yam reactive molecules. Muaj ntau qhov kev tshawb fawb txog kev tiv thaiv neuroprotection thiab kev cawm ntawm neurons tom qab oxidative raug mob [3,4].
Txhawm rau txhim kho cov kev kho mob tshiab thiab kuaj xyuas cov kab mob uas tshwm sim los ntawm oxidative hlwb raug mob, nws yog ib qho tsim nyog yuav tsum nkag siab txog kev ua haujlwm ntawm lub hlwb ntawm lub hlwb thiab kev sib tham ntawm lawv. Astrocytes yog ib qho tseem ceeb rau lub hlwb homeostasis vim hais tias lawv muab khoom noj khoom haus rau cov neurons, tswj kev ncaj ncees ntawm cov ntshav-hlwb barrier, tswj synapse kev ua si, thiab txheej txheem cell metabolites [5].
Microglia yog qhov tseem ceeb vim tias lawv ua haujlwm raws li macrophages hauv lub hlwb thiab teb sai sai rau kev cuam tshuam hauv lub hlwb [6]. Lub hom phiaj ntawm kev sib cuam tshuam ntawm astrocytes, microglia, thiab lwm yam hlwb hlwb tuaj yeem ntes lossis rov qab oxidative raug mob, uas ua rau muaj kev tiv thaiv neuroprotection.
Cov kev kuaj mob tshwj xeeb glialcell-raws li kev kuaj mob uas kuaj pom glial cell signaling txoj hauv kev siv biomarkersor neuroimaging tuaj yeem txheeb xyuas cov tib neeg muaj kev pheej hmoo ntawm neuronal tsis ua haujlwm ntau dua ua ntej thiab ntau meej, thiab cov biomarkers no tuaj yeem tso cai rau kev saib xyuas ntawm oxidative kab mob thiab / lossis rov qab los.
Qhov kev tshuaj xyuas no qhia txog cov kev paub tam sim no ntawm lub cev lub cev thiab kev ua haujlwm ntawm astrocytes thiab microglia hauv cov lus teb rau oxidativestress, lawv cov kev cuam tshuam nrog neurons, thiab lawv cov peev xwm tiv thaiv kab mob.
2. Qhov tsis zoo ntawm lub hlwb rau Oxidative Stress
Kev ntxhov siab oxidative, uas tuaj yeem raug ntxias los ntawm ntau lub tswv yim, ua lub luag haujlwm tseem ceeb hauv kev tuag ntawm lub hlwb thiab lub hlwb tsis ua haujlwm thiab ua rau cov kab mob neurodegenerative, suav nrog Alzheimer's disease (AD), Parkinson's disease (PD), kev laus, thiab lwm yam kab mob neurodegenerative [7-9].
Lub hlwb xav tau ntau ntawm adenosine triphosphate (ATP) thiab siv ntau dua 25% ntawm cov piam thaj hauv cov ntshav thiab 20% ntawm tag nrho cov pa oxygen (O2) los tswj kev ua haujlwm ntawm neuronal [10,11]. Txawm li cas los xij, kev siv cov piam thaj tuaj yeem ua rau muaj kev ntxhov siab oxidative los ntawm kev ua kom cov proteins los ntawm kev tsim cov khoom siv glycation kawg, thiab kev siv cov pa oxygen tuaj yeem tsim tau ROS thiab reactive nitrogen hom (RNS) ntawm endogenousmechanisms thaum lub sij hawm cellular respiration [12,13].
ROS / RNS ntau lawm tshwm sim thaum lub sij hawm oxidative phosphorylation, thiab nce dawb radical ntau lawm plays ib tug tseem ceeb luag hauj lwm nyob rau hauv neuronal tuag. Thaum ROS / RNS ntau tshaj qhov kev tshem tawm ntawm cov kab mob antioxidant, cov protein ntau degradation, lipid oxidation, thiab DNA degeneration tshwm sim thiab tom qab induce ib tug ntau dhau thiab pathological poob ntawm neurons [14,15].
Lub luag haujlwm tseem ceeb ntawm oxidative cell tuag yog tsim ntawm ROS thiab mitochondria tsis ua haujlwm.
Ib leeg-electron cov tshuaj tiv thaiv tsim cov tshuaj tiv thaiv kab mob raws li cov khoom tsis xav tau ntawm kev ua pa lossis ua rau muaj kev tiv thaiv ntau dhau. ROS/RNS suav nrog cov pa oxygen, superoxide anion radicals, hydroxyl radicals, hydrogen peroxide, nitricoxide, thiab peroxynitrite anions [16].
Cov molecules tsis ruaj khov no rhuav tshem cellular lipidsand proteins thiab thiaj li ua kom intracellular ROS ntau lawm ntawm nicotinamideadenine dinucleotide phosphate (NADPH) thiab electron thauj saw. Los ntawm cov cell membrane, NADPH yog siv los ua tus neeg pub khoom siv hluav taws xob rau kev hloov hluav taws xob thiab, thaum kawg, molecular oxygen raug txo rau ROS [17].
Lub mitochondria yog qhov chaw tseem ceeb ntawm kev tsim khoom ntawm intracellular ROS thiab lub hom phiaj ntawm kev raug mob ROS. Kev hloov hluav taws xob qeeb qeeb thaum lub sij hawm ua pa ua pa ua rau ROS ntau lawm thiab ua rau lub cev puas tsuaj loj [18]. Secondary mechanisms ntawm cell tuag ntawm ROS ntau lawm yog excitotoxicity, hlau metabolism, cytokines, pyroptosis, thiab necroptosis.
Kev tso tawm ntau dhau ntawm glutamate thiab kev nkag mus ntawm Ca2+ ua rau calcium overload hauv neurons thiab cuam tshuam hauv intracellularCa2+ homeostasis, uas tuaj yeem ua rau excitotoxicity los ntawm kev ua rau ROS ntau lawm [19].Iron-dependent oxidative stress kuj ua rau lub hlwb ua haujlwm tsis zoo. Thaum ib qho overload ntawm hlau overwhelms lub cell lub detoxification systems, hlau cov ntsiab lus (tshwj xeeb tshaj yog Fe2+) nce thiab txhawb kev hloov ntawm H2O2 rau •OH los ntawm Fenton cov tshuaj tiv thaiv, yog li amplifying oxidative kev nyuaj siab [20].
Inflammatory cells, tiv thaiv kab mob, thiab chemokines tuaj yeem tso cov tshuaj tiv thaiv kab mob thiab cytokines uas exacerbate oxidative kev nyuaj siab thiab cuam tshuam cov neurons.Microglia, uas yog ib qho tseem ceeb rau redox stability, qhib NADPH oxidase (NOX) andnitric oxide synthase (NOS) enzymes, ua rau muaj zog ntau lawm. ROS and RNS [21,22]. Astrocytes txhawb kev ua kom muaj zog thiab kev loj hlob ntawm microglia, uas ua rau muaj ntau yam kab mob hauv lub hlwb. Pyroptosis yog lwm hom inflammatory programmed cell tuag.
Leucine-rich-repeat (NLR) pyrin-domain-containing3 (NLRP3) inflammasome signaling pathway that induces cell pyrolysis is triggered byROS tiam thaum lub hlwb raug mob [23]. NLRP3 inflammasome activation nyob rau hauv astrocytes thiab microglia induces inflammatory teb thiab neuronal tuag [24]. Intracellular ROSaccumulation tuaj yeem hloov cov proteins, qabzib, lipids, thiab nucleic acids ua rau lub cev tsis ua haujlwm thiab tuag.
Tumor necrosis factor (TNF)-induced necroptosis (programmed necrosis) kuj ua rau ROS tiam [25]. Cov txheej txheem pathophysiological ntawm cell tuag vim kev nyuaj siab oxidative tau piav qhia hauv daim duab 1.
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