Microglial Turnover in Ageing-Related Neurodegeneration: Therapeutic Avenue To Intervene in Disease Progression Part 1
Apr 23, 2023
Abstract
Microglia yog lub hlwb nyob hauv macrophages thiab qhov tseem ceeb ntawm cov kab mob neuroimmune uas ua rau muaj kev loj hlob ntawm lub hlwb, homeostasis, kev laus, thiab kev kho mob hauv nruab nrab paj hlwb (CNS). Sib nrug los ntawm lwm lub hlwb macrophages, lawv tuaj yeem hnov txog kev hloov pauv hauv lub hlwb microenvironment, ua haujlwm hauv tsev rau kev noj qab haus huv neuronal thiab muab kev tiv thaiv neuroprotection hauv lub cev ib txwm muaj. Microglia siv ib txheej ntawm cov noob rau cov haujlwm no uas cuam tshuam nrog cov cytokines proinflammatory. Nyob rau hauv teb rau tej stimuli, lawv tso cov proinflammatory cytokines, uas yuav ua puas thiab tua cov neurons ntawm neuroinflamation. Txawm li cas los xij, kev hloov pauv hauv microglial ua haujlwm yog cov kab mob pathophysiology hauv cov hnub nyoog ntsig txog cov kab mob neurodegenerative, xws li Alzheimer's, Parkinson's, Huntington's, thiab prion kab mob, nrog rau amyotrophic lateral sclerosis, frontotemporal dementia, thiab mob encephalopathy. Thaum lawv cov tub ceev xwm lossis kev ua haujlwm hauv tsev raug cuam tshuam loj heev, lawv ua rau cov mob neuropathological ntau dhau los ntawm kev txhawb nqa lawv txoj haujlwm tiv thaiv thiab los ntawm neuroinflamation. Ob peb txoj hauv kev tau koom nrog hauv kev ua haujlwm microglial, suav nrog Trem2, Cx3cr1, thiab progranulin txoj hauv kev, uas ua rau cov lus teb microglial inflammatory nyob rau hauv kev tswj thiab txhawb kev tshem tawm ntawm kev raug mob stimuli. Sij hawm dhau mus, qhov tsis txaus ntseeg hauv cov kab ke no ua rau kev tiv thaiv microglia ua kev puas tsuaj, pib lossis ua rau muaj kev puas tsuaj ntau ntxiv. Kho qhov tsis txaus ntseeg no tuaj yeem yog hom kev kho mob hauv cov kab mob neurodegenerative.
Ntsiab lus
microglia; neurodegeneration; neuroinflamation; macrophages; homeostasis;Cov txiaj ntsig Cistanche.
Nyem qhov no kom tau txaiscov teebmeem ntawm Cistanche
Taw qhia
Microglia yog lub hlwb nyob hauv parenchymal macrophages [1] uas txawv ntawm lwm cov hlwb hauv lub hlwb uas tsis yog parenchymal macrophagic thiab cov ntaub so ntswg macrophages [2,3]. Nyob rau hauv kev noj qab haus huv thiab ib puag ncig, microglia yog tus kheej-kho nrog tsis muaj kev koom tes ntau ntawm peripheral myeloid hlwb [4]. Tsis tas li ntawd, ~ 5 feem pua ntawm tag nrho cov hlwb ntawm neocortex feem ntau yog microglial [5]. Cov macrophages no muaj ib qho kev faib tawm thoob plaws hauv nruab nrab lub paj hlwb (CNS) parenchyma, nrog cov pej xeem ntawm kwv yees li 10 feem pua ntawm tag nrho cov hlwb hauv CNS. Tsis tas li ntawd, lawv tuaj yeem tsim ib daim phiaj cellular nrog lawv cov txheej txheem ramified thiab motile heev [6]. Thaum lub sij hawm kev loj hlob ntawm lub hlwb, microglia pab tsim neural circuits los ntawm modulating lub zog ntawm synaptic transmissions thiab sculpting neuronal synapses. Thaum hnov txog CNS raug mob, lawv dhau los ua phagocytic thiab tshem tawm cov kab mob microbes, cov khib nyiab ntawm tes, protein aggregates, lossis ib hom kev thuam CNS. Txawm li cas los xij, kev ua kom microglial tau tshaj tawm thaum lub sijhawm ntau lub paj hlwb [7,8], uas lawv tau ua si ob qho tib si muaj txiaj ntsig thiab ua rau muaj kev puas tsuaj, nyob ntawm seb muaj kab mob.
Kev ua haujlwm zoo ntawm microglia yog qhov tsim nyog rau kev hloov pauv ntawm neural circuits thiab synaptic muaj nuj nqi, tab sis lawv txoj kev koom tes hauv cov kab mob ntawm cov kab mob neurological ua rau muaj kev sib cav txog seb microglial activation puas muaj txiaj ntsig lossis tsis zoo. Nyob rau hauv teb rau CNS insults, microglia proliferate sai [9], tab sis lawv proliferation thiab turnover tus nqi nyob rau hauv homeostatic tej yam kev mob tsis tau muaj ntaub ntawv zoo. Sau qhov sib txawv ntawm kev tshawb fawb no tuaj yeem cais lawv los ntawm cov kab mob ua rau cov neeg ua haujlwm [10]. Ntau qhov kev tshawb fawb tau pom tias muaj txiaj ntsig zoo tab sis tsis sib haum xeeb, tsis tshua muaj lossis siab heev microglial turnover nyob rau hauv nas thiab tom qab lub hlwb [11-13], txawm hais tias qhov siv tau ntawm cov tswv yim no tau sib cav thiab txwv [14,15]. Txawm li cas los xij, kev nkag siab txog kev tswj hwm ntawm microglial cov neeg nyob hauv lub hlwb yog qhov tseem ceeb rau kev nkag siab txog lawv txoj haujlwm ntawm ntau theem ntawm hnub nyoog thiab cov kab mob uas muaj hnub nyoog. Hauv ib rooj plaub, tus qauv nas ntawm AD tau pom tias thaum ntxov ntawm tus neeg microglia tuaj yeem ua rau muaj kev hloov pauv mus ntev hauv lub neej, thaum microglial senescence yuav muaj lub luag haujlwm hauv hnub nyoog ntsig txog neurodegeneration [10]. Piv txwv li, stimulation ntawm lub hlwb lub cev tiv thaiv kab mob thaum lub sij hawm txoj kev loj hlob tuaj yeem ua rau muaj kev hloov mus ntev hauv microglial lub cev tiv thaiv kab mob [16,17], thiab kev laus thiab kev loj hlob ntawm microglia pab txhawb rau cov kab mob neurodegenerative [18].
Txawm li cas los xij, kev hloov pauv hauv microglial homeostasis thiab kev ua haujlwm thaum muaj hnub nyoog thiab cov hnub nyoog ntsig txog cov kab mob neurodegenerative tuaj yeem yog vim muaj kev hloov pauv hauv lub hlwb microenvironment lossis rau lub neej ntev ntawm microglia, muaj peev xwm tseem tsis meej. Yog li ntawd, tsab xov xwm no yuav tham txog qhov nthuav dav microglia lub luag haujlwm ntawm lub cev thiab kev hloov pauv vim raug kev thuam sib txawv hauv cov neeg muaj hnub nyoog ntsig txog neurodegeneration.
Cistanche ntsiav tshuaj
Molecular thiab Functional Background ntawm Microglia
Microglia yog cov tshuaj tiv thaiv kab mob hauv lub hlwb thiab npog yuav luag 5-12 feem pua ntawm CNS hlwb [19]. Tsis tas li ntawd, microglia tau koom nrog hauv homeostasis ntawm tus tswv tsev tiv thaiv kab mob thiab ua rau cov kab mob neurological [20,21]. Cov hlwb no yog mesenchymal, originating nyob rau hauv lub yolk sac, thiab tsis xav tau hematopoietic qia hlwb rau kev rov ua dua tshiab [13,22]. Lawv txoj sia nyob thiab kev saib xyuas yog nyob ntawm cytokines, suav nrog CSF1 thiab interleukin (IL)-34 [23], thiab ntawm cov ntsiab lus hloov pauv xws li IRF8 [22]. Txawm li cas los xij, microglia tuaj yeem txhais tau tias yog lub cev tiv thaiv kab mob hauv lub cev ntawm CNS uas yog los ntawm cov hlwb myeloid thiab nthuav tawm ntau cov noob, suav nrog Cx3cr1, CD11b, Iba1, thiab F4/80 [21]. Raws li kev paub dav dav ntawm microglial noob qhia thiab cov haujlwm tseem ceeb [21,24], qhov kev tshawb fawb no tau sim txiav txim siab txog microglial zog los ntawm lawv cov noob kab lus. Muaj peb lub luag haujlwm tseem ceeb ntawm microglia - hnov lawv ib puag ncig, tswj lub cev homeostasis, thiab tiv thaiv tus kheej hloov kho thiab exogenous injurious agents. Tsis tas li ntawd, cov haujlwm ib txwm muaj yog cov tswj hwm tseem ceeb ntawm tib neeg lub cev xeeb tub mus txog rau hnub nyoog laus.
Kev hnov qab yog qhov yuav tsum tau ua rau microglia ua haujlwm hauv tsev tu thiab tiv thaiv lawv tus tswv ntawm kev raug mob (Daim duab 1). Microglia tsim ib lub network uas nthuav dav thoob plaws hauv CNS. Lawv cov txheej txheem nyias muaj zog thiab ua haujlwm tsis tu ncua, tso cai rau lawv tshawb xyuas thaj chaw nyob ib puag ncig lawv lub cev ntawm tes txhua ob peb teev thiab nrawm nrawm rau kev raug mob focal [8,19]. Lub network no suav nrog kwv yees li ntawm 100 lossis ntau dua cov noob uas tsis tu ncua tshawb xyuas ib puag ncig lub cev ntawm tes thiab paub txog kev hloov pauv hauv lawv cov microenvironment [24–26]. Qhov kev nkag siab mRNA tau qhia tsis sib xws hauv microglia ntawm thaj chaw sib txawv ntawm lub hlwb, qhia tias txhua tus microglia muaj peev xwm ntawm kev hnov mob.
Qhov thib ob thiab tseem ceeb tshaj plaws ntawm microglial muaj nuj nqi yog physiological homeostasis. Qhov kev ua haujlwm no suav nrog kev hloov kho synaptic xws li CNS kev txhim kho thiab kev saib xyuas, neurodegeneration [27,28], phagocytosis ntawm cov neeg tuag lossis ua haujlwm tsis zoo ntawm cov hlwb hlwb lossis cov khib nyiab ntawm tes [29,30], lossis myelin homeostasis [31] (Daim duab 2). Tsis tas li ntawd, microglia qhib ntau txoj hauv kev uas ua rau neuroinflamation thiab tej zaum neurodegeneration. Hauv cov txheej txheem no, microglia cuam tshuam nrog astrocytes, thiab lawv cov kev sib cuam tshuam kuj tseem ceeb hauv kev tswj hwm homeostasis. Ntau cov tshuaj chemokine thiab chemoattractant tsev tu noob tau koom nrog hauv phagocytosis (Trem2), synaptic pruning, thiab kho dua tshiab (C1q thiab Cx3cr1) [24], thiab kev tsis sib xws hauv cov noob tu vaj tsev no tuaj yeem ua rau cov kab mob neurodegeneration.
Raws li cov neeg muaj kev tiv thaiv kab mob hauv lub cev, microglia tiv thaiv lawv tus tswv tawm tsam cov kab mob (Daim duab 1) cov kab mob raug mob nrog rau Ap, aggregated a-synuclein, mutant huntingtin (mHtt), kev hloov pauv (mPrp).Sc), thiab oxidized superoxide dismutase (SOD). Microglia activates ob peb receptors rau incite host defenses, xws li nthuav qhia Fc receptors, Hu-zoo li receptors (TLRs), thiab ob peb antimicrobial peptides nrog rau Camp thiab Ngp (24]. Yog li ntawd, microglia mus txog qhov chaw neuroinflammatory los ntawm kev tsim cov peripheral inflammatory cytokines xws li TNF. -a thiab IL-1 (33 34). Tsis tas li ntawd, cov txheej txheem no suav nrog cov tshuaj chemokines (piv txwv li, Ccl2 uas nrhiav cov hlwb ntxiv thiab ua haujlwm ua ke txhawm rau tshem tawm cov kab mob thiab ua kom lub hlwb ua haujlwm zoo hauv lub cev (35]. Txawm li cas los xij. Raws li microglia-induced neuroinflammation ua rau neurotoxicity thiab, nws thiaj li neurodegeneration.Thiab rau qhov tsis zoo ntawm qhov kev ua haujlwm ntawm microglial, noj qab haus huv neural microglia ib txwm ua haujlwm zoo los ntawm kev hnov, kev tu vaj tse, thiab tiv thaiv lawv tus tswv.
Microglia thiab Aging
Kev laus yog qhov tsis muaj tseeb, thiab ntau yam kev hloov pauv thiab kev ua haujlwm tshwm sim hauv lub hlwb nrog kev laus dua. Piv txwv li, lub paj hlwb poob tag nrho ntawm 2 mus rau 3 feem pua ntawm ib xyoo caum tom qab hnub nyoog 50. Qhov kev poob ntawm lub hnub nyoog tshwj xeeb cuam tshuam rau qhov ntim ntawm grey thiab dawb teeb meem nyob rau hauv prefrontal, parietal, thiab lub cev nqaij daim tawv ({{ 3}}]. Yog li ntawd, ib tug neeg maj mam poob qhov kev kawm nyuaj thiab poob rau hauv kev paub txog kev ua haujlwm (38,39]. Ntau qhov kev hloov pauv ntawm tes kuj tshwm sim hauv cov hlwb laus, xws li genomic instability, shortening ntawm telomeres thiab ua kom cov qog suppressor noob. Nws yog ib qho tsim nyog yuav tsum ua kom muaj qhov sib npaug ntawm cov cytokines pro- thiab tiv thaiv inflammatory, tab sis, lub hlwb kev laus zuj zus qhia qhov tsis txaus ntawm cov cytokine qib hauv cov lus teb. mus ntev raug rau lub cev, tshuaj, los yog lom kab mob, xws li ionic hluav taws xob, cov pa phem, thiab cov kab mob (40,41]. Cov kev tshawb fawb pom tau hais tias ntev raug rau endogenous los yog exogenous pathogens txo cov anti-inflammatory cytokine IL-10 (42. Nyob rau hauv sib piv, xws li raug kuj nce inflammatory cytokines xws li TNF-a thiab IL-1 nyob rau hauv lub CNS (43] thiab IL{17}} nyob rau hauv plasma (44. Tsis tas li ntawd, muaj zog inflammatory txheej txheem ua rau neuronal cell tuag thiab ib tug Kev tsis sib haum xeeb ntawm kev tshem tawm thiab kev tsim cov ROS, ua rau muaj kev puas tsuaj loj ntawm cov yas yas zoo ib yam (Daim duab 2 thiab 3). Ntau qhov kev hloov pauv hauv cov laus lub hlwb muaj xws li kev puas tsuaj hauv basal autophagy uas pib nrog kev ntxhov siab ntawm cellular. , suav nrog Atg5, Atg7, thiab Becn1 (45], thiab zoo li kev txo qis hauv Atg-proteins tau tshwm sim hauv cov laus nas lub hlwb. Hauv qhov sib piv, kev laus tau pom los txhim kho mTORC1 (45,46] thiab nrawm mTOR txo qis macroautophagy thiab txhawb kev sib sau ua ke. Cov ntaub ntawv no tau txais kev txhawb nqa los ntawm kev loj hlob sai ntawm neurodegeneration hauv Atg5- [47] thiab Atg7- depleted (48) nas. Microglia, raws li thawj kab ntawm tus tswv tsev tiv thaiv , xaiv qhib autophagy rau entrapthreatening molecules rau hauv autophagosomes thiab tshem lawv ntawm autophagic degradation. Piv txwv li, microglial TLR4-induced activation of nuclear factor kB (NF-KB) upregulatesp62/SOSTM1 signaling, uas degrades misfolded a-syn proteins ntawm autophagy thiab tiv thaiv midbrain dopaminergic neuronal poob (49]. Tsis tas li ntawd, kev laus- Kev kho kom haum xeeb hauv kev ua haujlwm microglial cuam tshuam kev tswj hwm microglial ntawm autophagy thiab txhawb kev poob ntawm neuronal.
Kev laus tau raug lees paub tias yog ib qho kev pheej hmoo tseem ceeb rau ntau yam neurodegenerative disir. xaj. Kev laus Advanced suav nrog ntau yam cim qhia txog kev pheej hmoo ntawm kev tsim neu. Cov kab mob degenerative xws li Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), thiab kab mob frontotemporal lobar (FID). Tsis tas li ntawd, microglial hlwb hloov nrog kev laus uas yog ib qho tseem ceeb ntawm kev pheej hmoo rau hnub nyoog txog kev loj hlob ntawm neurodegeneration Txawm hais tias cov kab mob neurodegenerative muaj ntau yam xwm txheej, thiab lawv cov complexity tseem tsis tau to taub zoo, muaj kev pom zoo rau kev tshawb fawb txog cov kab mob degenerative thiab hnub nyoog. hloov lawv tuaj yeem ua rau hauv neural microenvironment.
Kev laus ua rau muaj qhov sib txawv ntawm qhov siab heterogeneity hauv microglia, uas kuj yog ib qho phenotype ntawm cov kab mob sib txawv neurodegenerative 39]. Ntxiv mus, tus qauv ntawm microglial noob qhia hloov pauv nrog kev laus thiab cov kab mob neurodegenerative (50 Cov kev hloov pauv loj hauv cov laus microglia yog nce ntim ntawm soma, kev thim rov qab hauv cov txheej txheem, thiab poob hauv cov ntaub so ntswg tsis sib xws (51]. Tsis tas li ntawd, microglial activation slows nrog lub hnub nyoog. , txo kev hnov mob thiab cuam tshuam kev sib cuag ntawm synaptic (6) Cov txheej txheem ntawm kev laus microglial activation no txawv ntawm classical activation thiab raug xa mus rau microglial dystrophy; qhov anomalous activation feem ntau yuav rhiab heev. Tsis tas li ntawd, ib qho phenotype tshiab ntawm microglia tau raug txhais-tsaus microglia-tus yam ntxwv los ntawm condensed electron-dense cytoplasm thiab nucleoplasm, nuclear chromatin remodeling, thiab qib siab ntawm synaptic stripping kev ua ub no thiab oxidative stress [54,55]. Interestingly, cov phenomena. tsis tau tsuas yog tau pom nyob rau hauv microglial cov pej xeem cuam tshuam nrog kev ntxhov siab ntev lossis kab mob xws li AD tab sis kuj nyob rau hauv microglia hauv ib txwm muaj lub hlwb laus [54]. Txawm hais tias kev paub txog cov kev hloov pauv ntawm cov qauv molecular no tseem nyob rau hauv nws cov me nyuam mos, nws twb tau tsim tias kev laus microglia yog cov granular heev thiab nthuav tawm qhov tsis pom kev tsaus nti hauv kev npaj immunohistological. Lwm qhov kev hloov pauv phenotypic hauv cov laus microglia yog qhov tsis zoo lysosomal digestion. Qhov kev tsis zoo no feem ntau tsim nyog rau kev sib sau ntawm cov khoom tsis txaus ntseeg uas muaj lipofuscin thiab lwm yam autofluorescent pigments [56,57]. Yog li ntawd, kev siv cov tshuaj immunofluorescence los yog flow cytometry tau dhau los ua neeg paub txog cov kws tshawb fawb kom paub qhov txawv ntawm qhov qub thiab hnub nyoog microglia. Kev sib sau ntawm cov xim autofluorescent thiab lipofuscin tau ntseeg tias yog cov khoom lag luam ntawm cov txheej txheem pov tseg tsis zoo thiab tau lees tias muaj kev cuam tshuam ncaj qha rau ntau yam kab mob neurodegenerative, suav nrog AD [58,59].
Microglial hloov nrog lub hnub nyoog tsis ua raws li ib txoj kev tshwj xeeb tab sis, theej, hloov thoob plaws hauv ib lub neej; Tom qab ncav cuag ib lub hnub nyoog, qhov kev cuam tshuam yuav tshwm sim. Kev txheeb xyuas ntawm thaj tsam frontal cortex ntawm post-mortem lub hlwb noj qab haus huv thoob plaws ntau lub hnub nyoog (los ntawm cov tub ntxhais hluas mus rau cov neeg muaj hnub nyoog 80 xyoo) pom tias microglial gene markers sib sau ua ke rau hauv ib qho transcriptional module nyob rau hauv ib tug gene co-expression network [60], thiab tus qauv qhia no tsis zoo cuam tshuam nrog lub hnub nyoog. Lwm txoj kev tshawb fawb tau qhia tias cov noob uas encode microglia nto receptors rau neuronal thiab / lossis microglial crosstalk tau cuam tshuam tshwj xeeb. Ob peb lub hlwb hais txog kev hloov pauv, suav nrog RUNX1, IRF8, PU.1, thiab TAL1, yog tus tswv tswj hwm ntawm hnub nyoog-nyob ntawm microglial modulation [39]. Qhov no ua rau cov lus nug ntawm seb nws tseem ceeb npaum li cas los txheeb xyuas lub hnub nyoog ntawm cov noob caj noob ces nyob rau hauv cov neeg laus kom nkag siab txog cov kab mob neurodegenerative pathology. Kev txheeb xyuas thaum pib ntawm kev hloov pauv caj ces hauv nruab nrab lossis lig-hnub nyoog nruab nrab tuaj yeem cuam tshuam nrog ntau qhov kev pib mob neurodegeneration thiab yog li yuav pab kom muaj kab mob.
Herba Cistanche
Cov txiaj ntsig ntawm Cistanche Extract hauv kev txhim kho kev nco
Cistanche yog cov tshuaj suav tshuaj suav tshuaj uas tau siv ntau pua xyoo los kho ntau yam mob, suav nrog teeb meem nco. Cov kws tshawb fawb tau dhau los ua kev txaus siab rau lub peev xwm ntawm Cistanche extract raws li ib qho kev kho mob rau kev paub txog kev poob qis thiab kev nco, vim muaj cov pov thawj loj hlob los qhia tias cov tshuaj ntsuab tuaj yeem muab ntau yam txiaj ntsig rau lub hlwb kev noj qab haus huv.
Ib qho ntawm cov khoom tseem ceeb ntawm Cistanche extract yog echinacoside, uas tau pom tias muaj cov teebmeem neuroprotective, txhais tau tias nws pab tiv thaiv hlwb hlwb los ntawm kev puas tsuaj los ntawm oxidative kev nyuaj siab thiab o. Tsis tas li ntawd, echinacoside tuaj yeem ua rau muaj kev loj hlob ntawm cov paj hlwb, uas yog qhov tseem ceeb rau kev loj hlob thiab muaj sia nyob ntawm cov neurons hauv lub hlwb.
Ntau qhov kev tshawb fawb tau tshawb xyuas cov txiaj ntsig ntawm Cistanche extract hauv kev txhim kho kev nco, nrog cov txiaj ntsig tau zoo. Ib txoj kev tshawb fawb luam tawm nyob rau hauv Phau ntawv Journal of Ethnopharmacology pom tias kev kho mob nrog Cistanche extract txhim kho kev nco hauv cov nas nrog kev paub tsis meej vim yog scopolamine. Cov kws tshawb fawb tau xaus lus tias Cistanche extract tuaj yeem yog tus neeg sawv cev kho mob zoo rau kev tiv thaiv thiab kho kev nco tsis txaus.
Lwm txoj kev tshawb fawb luam tawm hauv phau ntawv xov xwm Nutrients tshuaj xyuas qhov cuam tshuam ntawm Cistanche extract ntawm kev paub txog kev ua haujlwm hauv cov tub ntxhais hluas noj qab haus huv. Cov neeg koom nrog uas tau txais Cistanche extract tau ntsib kev txhim kho hauv kev mloog, kev ua haujlwm nco, thiab lub sijhawm tshuaj tiv thaiv piv rau cov neeg siv cov placebo. Cov kws tshawb fawb tau qhia tias Cistanche extract yuav yog ib qho tseem ceeb ntxiv rau cov tib neeg nrhiav kev txhim kho kev txawj ntse.
Txawm hais tias qhov kev pom zoo no, kev tshawb fawb ntxiv yog xav tau kom nkag siab txog cov txiaj ntsig zoo ntawm Cistanche extract rau kev txhim kho kev nco. Nws tseem ceeb heev uas yuav tsum nco ntsoov tias thaum Cistanche extract zoo li muaj kev nyab xeeb, nws yuav muaj kev cuam tshuam nrog qee yam tshuaj thiab yuav tsum tsis txhob noj yam tsis tau ntsib kws kho mob ua ntej.
Cistanche ntxiv
Hauv cov ntsiab lus, thaum xav tau kev tshawb fawb ntxiv, kev tshawb fawb tam sim no qhia tias Cistanche extract yuav muaj peev xwm txhim kho kev nco. Nws cov khoom tiv thaiv neuroprotective, ua ke nrog nws lub peev xwm los txhawb cov paj hlwb loj hlob, ua rau nws muaj txiaj ntsig zoo rau kev paub txog kev poob qis thiab kev nco. Txawm li cas los xij, cov tib neeg xav noj Cistanche extract yuav tsum xub sab laj nrog lawv tus kws kho mob kom ntseeg tau tias muaj kev nyab xeeb thiab siv tau.
Cov ntaub ntawv
1. Krotti, A.; Ransohoff, RM Microglial Physiology, thiab Pathophysiology: Kev nkag siab los ntawm Genome-wide Transcriptional Profiling. Kev tiv thaiv 2016, 44, 505–515.
2. Ginhoux, F.; Greter, M.; Leboeuf, M.; Neeb, S.; Saib, P.; Gokhan, S.; Mehler, MF; Conway, SJ; Ng, LG; Stanley, ER; ua al. Kev tsom xam txoj hmoo pom pom tias cov neeg laus microglia tau los ntawm cov macrophages thaum ntxov. Science 2010, 330, 841–845.
3. Xu, J.; Raud, C.; Karjalainen, K. Feem ntau cov ntaub so ntswg-Resident Macrophages Tsuas yog Microglia tau muab los ntawm Fetal Hematopoietic Stem Cells. Kev tiv thaiv 2015, 43, 382–393.
4. Hashimoto, D.; Chaw, A.; Noizat, C.; Teo, P.; Beasley, MB; Leboeuf, M.; Becker, CD; Saib, P.; Nqe, J.; Lucas, D.; ua al. Cov ntaub so ntswg-tus neeg nyob hauv macrophages nws tus kheej tswj hwm hauv zos thoob plaws hauv lub neej laus nrog kev pab tsawg kawg nkaus los ntawm cov kab mob monocytes. Kev tiv thaiv 2013, 38, 792–804.
5. Pelvig, DP; Pakkenberg, H.; Stark, AK; Pakkenberg, B. Neocortical glial xov tooj ntawm tes hauv tib neeg lub hlwb. Neurobiol. Xyoo 2008, 29, 1754–1762.
6. Hefendehl, JK; Neher, JJ; Sühs, RB; Kohsaka, S.; Skodras, UA; Jucker, M. Homeostatic thiab raug mob-induced microglia tus cwj pwm hauv lub hlwb laus. Aging Cell 2014, 13, 60–69.
7. Colonna, M.; Butovsky, O. Microglia Function nyob rau hauv Central Nervous System thaum lub sij hawm noj qab haus huv thiab Neurodegeneration. Annu. Rev. Immunol. 2017, 35, 441–468.
8. Hickman, S.; Ib., S.; Sen, P.; Morsett, L.; ib. El Khoury, J. Microglia hauv neurodegeneration. Nat. Neurosci. 2018, 21, 1359–1369.
9. Gómez-Nicola, D.; Fransen, NL; Suzzi, S.; Perry, VH Txoj Cai ntawm microglial proliferation thaum lub sij hawm mob neurodegeneration. J. Neeb. Tawm. J. Soc. Neurosci. 2013, 33, 2481–2493.
10. Füger, P.; Hefendehl, JK; Veeraraghavalu, K.; Wendeln, AW; Schlosser, C.; Obermüller, UA; Wegenast-Braun, BM; Neher, JJ; Martus, P.; Kohsaka, S.; ua al. Microglia hloov pauv nrog kev laus thiab hauv Alzheimer tus qauv ntawm lub sijhawm ntev hauv vivo ib leeg-cell duab. Nat. Neurosci. 2017, 20, 1371–1376.
11. Lawson, LJ; Perry, VH; Gordon, S. Turnover ntawm cov neeg nyob hauv microglia hauv cov neeg laus nas lub hlwb. Neuroscience 1992, 48, 405–415.
12. Askew, K.; Li, K.; Olmos-Alonso, A.; Garcia-Moreno, F.; Liang, Y.; Richardson, P.; Tipton, T.; Chapman, MA; Riecken, K.; Beccari, S.; ua al. Coupled Proliferation thiab Apoptosis Tuav lub nrawm nrawm ntawm Microglia hauv cov neeg laus lub hlwb. Cell Rep. 2017, 18, 391–405. [CrossRef]
13. Tay, TL; Maiv, D.; Dautzenberg, J.; Fernandez-Klett, F.; Lin, G.; Daws, M.; Drouard, A.; Stempfl, T.; Ardura-Fabregat, A.; Staszewski, O.; ua al. Ib txoj hmoo tshiab qhia txog cov ntsiab lus-nyob ntawm qhov sib txawv lossis clonal nthuav ntawm microglia. Nat. Neurosci. Xyoo 2017, 20, 793–803.
14. Nowakowski, RS; Hayes, NL New neurons: Cov ntaub ntawv pov thawj tshwj xeeb lossis cov lus xaus txawv txawv? Science 2000, 288, 771.
15. Rakic, P. Neurogenesis nyob rau hauv cov laus primates. Prog. Lub hlwb Res. 2002, 138, 3–14.
16. Knuesel, I.; Chaw, L.; Britschgi, M.; ib. Schobel, SA; Bodmer, M.; ib. Hellings, JA; Toovey, S.; Prinssen, EP Maternal immune activation thiab kev loj hlob ntawm lub hlwb txawv txav thoob plaws CNS. Nat. Rev. Neurol. 2014, 10, 643–660.
17. Perry, VH; Holmes, C. Microglial priming nyob rau hauv cov kab mob neurodegenerative. Nat. Rev. Neurol. 2014, 10, 217–224.
18. Streit, WJ; Xu, QS; Tischer, J.; Bechmann, I. Microglial pathology. Acta Neuropathol. Pawg. Xyoo 2014, 2, 142.
19. Lawson, LJ; Perry, VH; Dri, P.; Gordon, S. Heterogeneity nyob rau hauv kev faib thiab morphology ntawm microglia nyob rau hauv ib txwm neeg laus nas hlwb. Neuroscience 1990, 39, 151–170.
20. El Khoury, J. Neurodegeneration thiab cov kab mob neuroimmune. Nat. Med. 2010, 16, 1369–1370.
21. Ransohoff, RM; El Khoury, J. Microglia hauv Kev Noj Qab Haus Huv thiab Kab Mob. Caij nplooj ntoos hlav Harb. Kev xav. Biol. Xyoo 2015, 8, 020560.
22. Kierdorf, K.; Erny, D.; Goldmann, T. Sander, V.; Schulz, C.; Perdiguero, EG; Wieghofer, P.; Heinrich, UA; Riemke, P.; Hölscher, C.; ua al. Microglia tshwm sim los ntawm erythromyeloid precursors ntawm Pu.1- thiab Irf8- txoj hauv kev. Nat. Neurosci. 2013, 16, 273–280.
23. Wang, Y.; Szrter, KJ; Vim, W.; Gilfillan, S.; Rossini, C.; ib. Cella, M.; Barrow, AD; Pob zeb diamond, MS; Colonna, M. IL-34 yog cov ntaub so ntswg txwv ligand ntawm CSF1R xav tau rau kev loj hlob ntawm Langerhans hlwb thiab microglia. Nat. Immunol. 2012, 13, 753–760.
24. Hickman, SE; Kingery, ND; Ohsumi, TK; Borowsky, ML. Wang, LC; txhais tau tias, TK; El Khoury, J. Qhov kev nkag siab microglial tau tshwm sim los ntawm kev ncaj qha RNA sequencing. Nat. Neurosci. 2013, 16, 1896–1905.
25. Haynes, SE; Hollopeter, G.; Yaj, G.; Kurpius, D.; Dailey, ME; Gan, WB; Julius, D. P2Y12 receptor regulates microglial activation los ntawm extracellular nucleotides. Nat. Neurosci. 2006, 9, 1512–1519.
26. Fourgeaud, L.; Través, PG; Tug, Y.; Leal-Bailey, H.; Lew, ED; Burrola, PG; Callaway, P.; Zagórska, UA; Rothlin, CV; Nimmerjahn, A.; ua al. TAM receptors tswj ntau yam ntawm microglial physiology. Xwm Txheej 2016, 532, 240–244.
27. Vasek, MJ; Garber, C.; Dorsey, D.; Durrant, DM; Bolman, IB; Saub, A.; Yog, J.; Perez-Torres, C.; Frauin, A.; Wilton, DK; ua al. Ib qho ntxiv-microglial axis drives synapse poob thaum lub sij hawm tus kab mob ua rau tsis nco qab. Xwm Txheej 2016, 534, 538–543.
28. Lui, H.; Zhang, J. Makinson, SR; Cahill, MK; Kelley, KW; Huang, HY; Tsau, Y.; Oldham, MC; Martens, LH; Gao, F.; ua al. Progranulin Deficiency txhawb nqa Circuit Court-Specific Synaptic Pruning los ntawm Microglia ntawm kev ua kom tiav. Cell 2016, 165, 921–935.
29. Fuhrmann, M.; Bittner, T.; Jung, CK; Burgold, S.; Page, RM; Mitteregger, G.; Hais, C.; LaFerla, FM; Kretzschmar, H.; Herms, J. Microglial Cx3cr1 knockout tiv thaiv neuron poob hauv tus nas qauv ntawm Alzheimer's kab mob. Nat. Neurosci. 2010, 13, 411–413.
30. Krasemann, S.; Madore, C.; Cialis, R.; Baufeld, C.; ib. Calcagno, N.; El Fatimy, R. Beckers, L.; ib. O'Loughlin, E.; Xu, Y.; Fanek, Z.; ua al. Lub TREM2-APOE Txoj Kev Tsav Tsheb Hloov Cov Phenotype ntawm Dysfunctional Microglia hauv Cov Kab Mob Neurodegenerative. Kev tiv thaiv 2017, 47, 566–581.
31. Healy, LM; Perron, G.; Yeej, SY; Michell-Robinson, MA; Rezk, A.; Ludwin, SK; Moore, CS; Hall, JA; Bar-los, A.; Antel, JP MerTK yog Tus Txheej Txheem Ua Haujlwm ntawm Myelin Phagocytosis los ntawm Tib Neeg Myeloid Cells. J. Immunol. 2016, 196, 3375–3384.
32. Pasciuto, E.; Burton, OT; Roca, CP; Laug, V.; Rajan, WD; Lawv, T.; Mancuso, R.; Tito, RY; Koj, L.; Callaerts-Vegh, Z.; ua al. Microglia Yuav tsum tau CD4 T Cells kom tiav kev hloov ntawm fetal-rau-laus. Cell 2020, 182, 625–640.
33. El Khoury, JB; Moore, KJ; txhais tau tias, TK; Leung, J.; Terada, K.; Taub, M.; Freeman, MW; Luster, AD CD36 kho cov lus teb tus tswv tsev innate rau beta-amyloid. J. Exp. Med. 2003, 197, 1657–1666.
34. Hickman, SE; Allison, EK; El Khoury, J. Microglial dysfunction thiab defective beta-amyloid clearance pathways in aging Alzheimer's disease nas. J. Neeb. Tawm. J. Soc. Neurosci. Xyoo 2008, 28, 8354–8360.
35. El Khoury, J.; Taub, M.; Hickman, SE; txhais tau tias, TK; Terada, K.; Geula, C.; Luster, AD Ccr2 deficiency impairs microglial tsub zuj zuj thiab accelerates kev loj hlob ntawm Alzheimer-zoo li tus kab mob. Nat. Med. Xyoo 2007, 13, 432–438.
36. Ib., Y.; Grossman, RI; Babb, JS; Raub, ML; Mannon, LJ; Kolson, DL Hnub nyoog ntsig txog tag nrho cov teeb meem grey, thiab cov teeb meem dawb hloov pauv hauv cov neeg laus lub hlwb. Ntu I: Volumetric MR duab tsom xam. Ajar. Am. J. Neuroradiol. 2002, 23, 1327–1333.
37. Sowell, ER; Peterson, IB; Thompson, PM; Txais tos, SE; Henkenius, AL; Toga, AW Mapping cortical hloov thoob plaws tib neeg lub neej. Nat. Neurosci. 2003, 6, 309–315.
38. Salat, DH; Buckner, RL; Snyder, AZ; Greve, DN; Desikan, RS; Busa, E.; Morris, JC; Dale, AM; Fischl, B. Thinning ntawm cerebral cortex hauv kev laus. Cerebral Cortex 2004, 14, 721–730.
39. Von Bernhardi, R.; Eugenín-von Bernhardi, L. Eugenín, J. Microglial cell dysregulation hauv hlwb laus thiab neurodegeneration. Pem hauv ntej. Kev laus Neurosci. Xyoo 2015, 7, 124.
40. Dröge, W.; Schipper, HM Oxidative stress thiab aberrant signaling nyob rau hauv kev laus thiab kev txawj ntse poob. Aging Cell 2007, 6, 361–370. [CrossRef] 41. Vijg, J.; Campisi, J. Puzzles, kev cog lus thiab kev kho rau kev laus. Xwm Txheej 2008, 454, 1065–1071.
42. Zhou, B.; Bailey, WM; Braun, KJ; Gensel, JC Hnub nyoog txo qis macrophage IL-10 qhia: cuam tshuam rau kev ua haujlwm rov qab thiab kho cov ntaub so ntswg hauv kev raug mob qaum qaum. Exp. Neurol. 2015, 273, 83–91.
43. Lukiw, WJ Gene qhia profileing nyob rau hauv fetal, laus, thiab Alzheimer hippocampus: Ib qho txuas ntxiv ntawm kev ntxhov siab ntsig txog kev taw qhia. Neurochem. Res. 2004, 29, 1287–1297.
44. Godbout, JP; Chen, J.; Abraham, J.; Richwine, AF; Berg, IB; Kelley, KW; Johnson, RW Exaggerated neuroinflammation thiab kev mob tus cwj pwm hauv cov nas muaj hnub nyoog tom qab ua kom lub cev tiv thaiv kab mob peripheral. Faseb J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2005, 19, 1329–1331.
45. Aws, C.; Koj, J.; Hoob, A.; Jung, T.; Grune, T. Macroautophagy yog impaired nyob rau hauv qub murine hlwb cov ntaub so ntswg raws li nyob rau hauv senescent tib neeg fibroblasts. Redox Biol. 2016, 10, 266–273.
46. Plaza-Zabala, A.; Sierra-Torre, V.; Sierra, A. Autophagy thiab Microglia: Novel Partners in Neurodegeneration and Aging. Int. J. Mol. Sci. Xyoo 2017, 18, 598.
47. Hara, T.; Nakamura, K.; Matsui, M.; Yamamoto, A.; Nakahara, Y.; Suzuki-Migishima, R.; Yokoyama, M.; Mishima, K.; Saito, I.; Okano, H.; ua al. Kev tshem tawm ntawm basal autophagy hauv cov hlwb neural ua rau cov kab mob neurodegenerative hauv nas. Xyoo 2006, 441, 885–889.
48. Komatsu, M.; Waguri, S.; Chib, T.; Murata, S.; Ib, J.; Tanida, I.; Ueno, T.; Koj, M.; Uchiyam, Y.; Kominami, E.; ua al. Kev poob ntawm autophagy nyob rau hauv lub hauv paus paj hlwb ua rau neurodegeneration hauv nas. Xyoo 2006, 441, 880–884.
49. Choi, I.; Zhang, YJ; Seegobin, SP; Pruvost, M.; Wang, Q.; Purtell, K.; Zhang, IB; Yue, Z. Microglia ntshiab neuron-tso tawm -synuclein ntawm xaiv autophagy thiab tiv thaiv neurodegeneration. Nat. Pawg. Peb Hlis 2020, 11, 1386.
50. Holtman, IR; Raj, DD; Miller, JA; Schaafsma, W. Yin, Z.; Brouwer, N.; Wes, PD; Möller, T. Rau, M.; Kampuis, W.; ua al. Induction ntawm ib hom microglia noob qhia kos npe los ntawm kev laus thiab cov kab mob neurodegenerative: Ib qho kev qhia meta-kev tshuaj xyuas. Acta Neuropathol. Pawg. Xyoo 2015, 3, 31.
51. Wong, WT Microglial aging in the healthy CNS: Phenotypes, drivers, and rejuvenation. Pem hauv ntej. Cell. Neurosci. Xyoo 2013, 7, 22.
52. Streit, WJ; Braak, H.; Xu, QS; Bechmann, I. Dystrophic (senescent) es tsis yog lub hlwb ua kom muaj zog microglial yog txuam nrog tau pathology thiab tej zaum yuav ua ntej neurodegeneration hauv Alzheimer's kab mob. Acta Neuropathol. 2009, 118, 475–485.
53. Streit, WJ; Sammons, NW; Kuhns, AJ; Sparks, DL Dystrophic microglia hauv cov laus tib neeg lub hlwb. Glia 2004, 45, 208–212.
54. Bisht, K.; Sharma, KP; Lecours, C.; Sánchez, MG; El Hajj, H.; Milior, G.; Olmos-Alonso, A.; Gómez-Nicola, D.; Luheshi, G.; Vallières, L.; ib. ua al. Tsaus microglia: Ib qho phenotype tshiab feem ntau cuam tshuam nrog cov xeev pathological. Xyoo 2016, 64, 826–839.
55. Koellhoffer, EC; McCullough, LD; Ritzel, RM Qub Maids: Kev Laus thiab Nws cuam tshuam rau Microglia Function. Int. J. Mol. Sci. Xyoo 2017, 18, 769.
56. Nakanishi, H.; Wu, Z. Microglia-aging: Lub luag haujlwm ntawm microglial lysosome- thiab mitochondria-derived reactive oxygen hom hauv hlwb laus. Behav. Lub hlwb Res. 2009, 201, 1–7.
57. Mas, RE; Griffin, ST; Graham, DI Aging-associated hloov pauv hauv tib neeg lub hlwb. J. Neuropathol. Exp. Neurol. 1997, 56, 1269–1275.
58. Grey, DA; Woulfe, J. Lipofuscin thiab kev laus: Ib qho teeb meem ntawm cov khib nyiab pov tseg. Sci. Aging Knowl. Ib puag ncig. Sage Ke 2005, 2005, re1.
59. Ahmed, Z.; ib. Sheng, H.; Xu, YF; Lin, WL; Innes, AW; Gas, J.; yus, X.; Wuertzer, CA; Hu, H.; Chib, S.; ua al. Accelerated lipofuscinosis thiab ubiquitination hauv granulin knockout nas qhia lub luag haujlwm rau progranulin hauv kev laus ua tiav. Am. J. Pathol. 2010, 177, 311–324.
60. Wehrspaun, CC; Haerty, W.; Ponting, CP Microglia recapitulate ib hematopoietic master regulator network nyob rau hauv cov laus tib neeg frontal cortex. Neurobiol. Hnub nyoog 2015, 36, 2443.e9–2443.e20.
