Lwm Lub Hom Phiaj Los Tawm tsam Alzheimer's Disease: Tsom Rau Astrocytes Part 2

2.3. Unfolded Protein teb thiab tsis muaj Proteostasis

AD yog cov kab mob neurological uas tshwm sim los ntawm kev sib koom ua ke ntawm misfoldedand aggregated proteins, uas nws lub luag hauj lwm nyob rau hauv lub pathogenesis thiab kev loj hlob ntawm tus kab mob tseem tsis meej.

Lub paj hlwb yog lub chaw tswj hwm ntawm tib neeg lub hlwb. Nws yog ib tug complex system lub luag hauj lwm rau kev ua hauj lwm ntawm tag nrho cov qhov chaw ntawm peb lub cev. Cov kab ke no suav nrog peb txoj kev xav, kev ua, kev xav, kev nco, thiab lwm yam. Lub paj hlwb noj qab haus huv yog qhov tseem ceeb rau kev tswj lub cev ua haujlwm ntawm lub cev thiab txhim kho kev nco.

Ntau tus neeg ntsib cov kab mob neurological, xws li Alzheimer's lossis Parkinson's disease. Cov kab mob no tuaj yeem cuam tshuam rau tib neeg lub neej zoo, tab sis tsis tau txhais hais tias lawv tsis tuaj yeem muaj kev nco zoo. Muaj ntau txoj hauv kev los txhim kho thiab txhim kho kev nco, txawm tias nyob rau hauv lub ntsej muag ntawm cov kab mob no.

Ua ntej, nws yog ib qho tseem ceeb heev uas yuav tsum tau hais kom nce ntau zaus thiab kev siv lub hlwb. Qhov no tuaj yeem ua tiav los ntawm ntau yam kev txawj ntse, xws li nyeem phau ntawv, daws cov kev sib tw, kawm lus tshiab, lossis ua si parkour games. Cov kev tshawb fawb tau pom tias cov dej num no tuaj yeem ntxiv dag zog rau lub hlwb kev sib koom tes, txhim kho kev xav, thiab txhim kho lub hlwb kom pom tseeb, yog li txhim kho kev nco.

Qhov thib ob, kev noj zaub mov zoo thiab pw tsaug zog kuj tseem ceeb heev. Qee cov zaub mov, xws li ntses thiab chia noob, muaj nplua nuj nyob rau hauv Omega -3 fatty acids, uas pab txhawb lub hlwb noj qab haus huv. Ntawm qhov tod tes, kev pw tsaug zog tseem ceeb heev rau lub hlwb rov qab vim tias kev pw tsaug zog pab txhawb kev nco thiab khaws cov ntaub ntawv tshwj xeeb.

Thaum kawg, nws yog ib qho tseem ceeb kom ua kom koj tus cwj pwm zoo. Kev ntxhov siab ntev, kev txhawj xeeb, ntshai, thiab lwm yam kev xav tuaj yeem cuam tshuam rau tib neeg lub cim xeeb. Ntawm qhov tsis sib xws, los ntawm kev xyaum ua kom xav, yoga lossis lwm yam kev so, kev ntxhov siab thiab kev ntxhov siab tuaj yeem txo, uas tuaj yeem pab txhim kho kev nco.

Feem ntau, cov kab mob neurological tsis tuaj yeem tiv thaiv peb kom tsis txhob muaj kev nco zoo. Los ntawm kev siv cov kev ntsuas zoo, peb tuaj yeem txhim kho peb lub hlwb ua haujlwm thiab txhawb nqa lub paj hlwb noj qab haus huv, yog li ua tiav lub neej zoo thiab nco zoo dua. Nws tuaj yeem pom tau tias peb yuav tsum txhim kho kev nco, thiab Cistanche tuaj yeem txhim kho kev nco zoo vim Cistanche muaj cov tshuaj tiv thaiv antioxidant, tiv thaiv kev laus, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidative thiab inflammatory teb nyob rau hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv ntawm lub hlwb. 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

Txawm li cas los xij, nws yog qhov tsim nyog rau kev xav tias qhov ua haujlwm tsis zoo ntawm cov protein homeostasis (proteostasis) tshwm sim. Proteostasis yog qhov nyuaj vim nws xav tau cov proteins kom nyob rau hauv ib qho chaw tshwj xeeb, sib sau ua ke, concentration, thiab conformation.

Ntau qhov xwm txheej tshwm sim hauv AD tau raug pom zoo los ua cov proteostasis perturbators, suav nrog NFTs [86], neuroinflammation [87], hloov pauv calcium signaling [88], mitochondrial zog tsis txaus [89], thiab oxidative stress [90].

Feem ntau ntawm cov no tau txuas nrog endoplasmicreticulum (ER) kev nyuaj siab [91]. ER yog ib qho tseem ceeb organelle nyob rau hauv eukaryotes lub luag hauj lwm rau lub synthesis thiab folding ntawm tag nrho cov secretory thiab membrane proteins [92].

Raws li physiological tej yam kev mob, thaum aberrant proteins yog synthesized, lub ER xa lawv mus rau lub cytosol, qhov twg lawv raug coj mus rau lub ubiquitin-proteasome system rau degradation [93].

Nyob rau hauv AD, qhov loj ntawm cov protein ntau ntawm cov misfolded ntawm ER koom nrog cov lus teb unfoldedprotein (UPR), ib qho kev cuam tshuam cov teeb meem kev ntxhov siab uas orchestratesprotein folding thiab pib apoptosis, lossis autophagy, hauv irreversibly puas hlwb [94]. Cov pov thawj loj hlob qhia tias ER Cov lus teb kev ntxhov siab kuj tseem tuaj yeem cuam tshuam cov kab mob metabolic uas tsim A, qhia nws txoj haujlwm ncaj qha hauv AD etiology.

Piv txwv li, nws tau pom tias UPR teeb liab cov xwm txheej nce BACE1 qib, ua rau A overproduction thiab txhawb cov transcription ntawm PSEN gene [95].

2.4. Ntxiv Cascade thiab Neuroinflamation

Kev mob tshwm sim tau raug lees paub tias yog ib feem tseem ceeb ntawm AD pathology [96], yuav muaj feem cuam tshuam txog kev kis tus kab mob [97,98]. Ntau qhov kev hloov pauv uas cuam tshuam nrog cov lus teb inflammatory tau pom muaj feem cuam tshuam nrog AD.

Piv txwv li, CCAAT/enhancer-binding protein (c/EBP) tsev neeg ntawm cov ntaub ntawv hloov pauv tau nce siab hauv lub hlwb ntawm cov neeg mob AD, piv rau kev tswj hwm kev noj qab haus huv [99], thiab nws tau pom los txhawb cov kab mob neuroinflammatory teb [100]. Lwm qhov piv txwv yog NF-kB txoj hauv kev uas tswj cytokine ntau lawm thiab cell ciaj sia taus, uas muaj feem xyuam nrog ADneuroinflammation [101].

Ob qho tib si classical thiab lwm txoj hauv kev ntxiv yog induced hauv vitro los ntawm fibrillar A [102] thiab NFTs [103]. Senile plaques colocalize nrog microglia thiab ntau cov proteins ntawm qhov sib ntxiv cascade nyob rau hauv cov tsiaj qauv ntawm tus kab mob thiab tib neeg AD [62,104-106].Tsis tas li ntawd, tib neeg lub hlwb AD qhia cov cim ntawm kev ua kom muaj kev sib ntxiv hauv tib thaj chaw uas nthuav tawm cov plaques senile thiab NFTs [107].

Cov ntsiab lus ntxiv tau nce siab thaum lub sij hawm AD kev loj hlob, zoo li feem ntau cov tshuaj tiv thaiv rau cov protein ntau txawv txav thiab lwm yam kev raug mob ntawm lub hlwb uas tshwm sim hauv AD hlwb [108-110].

Qhov no tsis yog qhov xav tsis thoob, vim tias qhov sib ntxiv cascade yog qhov tseem ceeb ntawm lub cev tiv thaiv kab mob hauv lub cev uas nyiam kev tshem tawm sai ntawm cov kab mob, apoptotic hlwb, thiab lawv cov khib nyiab, nrog rau qhov ntev thiab kev txiav tawm ntawm lub cev tiv thaiv kab mob [111]. Qee cov khoom ntawm qhov sib ntxiv cascade ua lub luag haujlwm tseem ceeb hauv synapse pruning.

Cov txheej txheem no yog active thiab tseem ceeb thaum lub sij hawm kev loj hlob ntawm lub paj hlwb. Txawm li cas los xij, nws tsis tshua pom nyob rau hauv cov neeg laus lub hlwb thaum nws qhov tshwm sim yog xav tias yuav ua rau muaj kev puas tsuaj, xws li hauv AD hlwb.Xwb, cov pov thawj ntawm kev sib koom ua ke ntau dhau ntawm cov synapse pruning tau tshaj tawm hauv AD thiab tsiaj qauv ntawm kev laus [112-114].

Txawm li cas los xij, qee cov ntaub ntawv pov thawj tib neeg qhia qhov tsis sib xws ntawm cov ntshav thiab cerebrospinal kua (CSF) cov ntsiab lus ntawm cov protein sib xyaw ua ke [110], qhia txog cov heterogenicity ntawm cov kab mob pathology, uas cuam tshuam rau txoj kev siv cov protein ntxiv raws li kev kuaj mob biomarkers. Txawm li cas los xij, cov khoom ntawm cov khoom ntxiv tuaj yeem yog cov hom phiaj kho tshiab [111,115].

Hauv cov qauv preclinical ntawm cov kab mob neurodegenerative, qhov inhibition ntawm cov protein ntau ntxiv tau txais txiaj ntsig zoo [116,117]. Hmoov tsis zoo, ntshav-hlwb barrier (BBB) ​​tsis tuaj yeem nkag mus rau cov kev kho mob tam sim no, ua rau kev tsim tshuaj nyuaj [117]. Tsis tas li ntawd, cov txheej txheem molecular hauv qab cov txheej txheem inflammatory tau pom hauv AD tseem tsis tau qhia meej meej.

Qhov no tuaj yeem piav qhia txog qhov tsis ua tiav ntawm qhov kev sim tshuaj ntsuam xyuas tau ua dhau los ua cov tshuaj tiv thaiv kab mob sib xyaw ua ke [118–122].Neuroinflammation yog cov txheej txheem tiv thaiv nyuaj tseem ceeb heev rau kev khaws cia ntawm lub hlwb homeostasis uas ua rau muaj kev puas tsuaj nyob rau qee qhov xwm txheej, uas tsis nkag siab zoo.

Tam sim no nws tau lees paub tias txhua qhov kev thuam ntawm lub hlwb ua rau ua rau lub hlwb ua haujlwm ntawm cov hlwb hauv kev tiv thaiv, cov txheej txheem khaws cia los ntawm kev rov ua kom cov homeostasis ploj.Ob qho kev hloov kho morphological thiab kev ua haujlwm ntawm feem ntau, tab sis tsis yog tshwj xeeb, microglia thiab astrocytes tshwm sim nrog ib puag ncig tiv thaiv [19 ].

Microgliacells, yog lub cev tiv thaiv kab mob ntawm lub hauv nruab nrab paj hlwb (CNS), yog thawj cov hlwb teb nrog cov lus teb muaj zog, yog li ua rau ua rau lwm hom glial cell, suav nrog astrocytes [123,124].

Yog hais tias cov stimuli uas qhib glialcells yog khaus heev, thiab / los yog kav ntev, thiab / los yog tsis counterbalanced los ntawm ib tug interruptionsignal, reactive gliosis yuav raug tsim thiab ib txwm lub hlwb ua hauj lwm yuav bealtered, ua rau txawm mus rau neuronal tuag [125]. Txawm li cas los xij, lub sijhawm thiab cov txheej txheem uas tig neuroinflamation los ntawm lub cev mus rau cov txheej txheem pathological tseem tsis tau kawm [126,127].

Yog li ntawd, qhov kev qhia meej ntawm lub hauv paus molecular thiab cellularmechanisms tuaj yeem tso cai rau cov kws tshawb fawb los tsim thiab sim tshiab, thiab cia siab tias yuav muaj txiaj ntsig zoo, kho tshuaj kho mob. Piv txwv li, ib txoj kev tshawb fawb tsis ntev los no tau txheeb xyuas qhov tsis zoo ntawm qhov kev hloov pauv ntawm c / EBPb, lub luag haujlwm rau microglia-mediated neuroinflammation, uas tuaj yeem sawv cev rau lub hom phiaj kho mob tshiab AD [100].

Nco ntsoov, c / EBPb yog qhia los ntawm astrocytes. Yog li, kev tshawb fawb ntxiv yuav tsum hais txog qhov muaj peev xwm ntawm kev tsom mus rau hauv ntau hom cell koom nrog hauv cov txheej txheem neuroinflammatory.

2.5. Lub Neuroenergetic Hypothesis

Glucose yog lub hlwb lub zog tseem ceeb roj, uas hla BBB los ntawm GLUT1, amembrane-bound glucose transporter. Ob qho kev laus thiab AD yog txuam nrog kev txo qis ntawm GLUT1 [128,129].

Tsis tas li ntawd, cov qauv transgenic nas qhia kev sib raug zoo ntawm qhov txo qis ntawm GLUT1 thiab A peptide txuam nrog [129,130]. Hauv cov neeg laus, kev sib koom ua ke ntawm cov piam thaj hypometabolism thiab apoE genotype tau ua [131] .Lub ntsiab lus qhia tias kev kho kom haum xeeb ntawm cov piam thaj hauv cov hlwb yog kev cuam tshuam ntawm pancreatic hormone insulin nrog nws cov receptor.

Cov neeg mob AD demented qhia txog qib siab ntawm plasma insulin, thaum qib qis ntawm CSF insulin thiab hlwb hlwb receptors. Kev tsis sib haum xeeb, insulin tsis kam tau cuam tshuam nrog kev dementia, thiab cov neeg mob uas muaj hom -2 mob ntshav qab zib mellitus muaj kev pheej hmoo ntau dua ntawm kev tsim AD [132]. Qhov tseeb, cov piam thaj ua rau kev nco qab vim tias cov haujlwm neuronal yog nruj ua ke rau kev siv cov piam thaj [133].

Siv 5xFAD nas ua tus qauv AD, Andersen li al. qhia tau hais tias neuronal GABA synthesis nyob rau hauv lub hlwb yog ncaj qha cuam tshuam los ntawm qabzib hypometabolism nyob rau hauv astrocytes [134]. Raws li ib txwm muaj, astrocytes tsim ATP thiab lactate uas tau tso tawm los pub cov neeg nyob sib ze, hauv cov txheej txheem hu ua astrocyte-neuron lactate shuttle, uas txhawb nqa cov neurons tau muab lawv cov kev xav tau siab zog, xws li kev ua haujlwm tua hluav taws [135-137] .

Qhov no yog qhov tsim nyog rau kev muaj peev xwm mus sij hawm ntev [135]. Berchtold et al. tau tshaj tawm tias ntau cov noob koom nrog hauv mitochondrial bioenergetics tau tswj hwm hauv cov neeg laus uas muaj kev paub tsis meej (MCI), txheeb ze rau cov hnub nyoog sib xws, tab sis txo qis cov neeg mob AD [138]. Tag nrho cov pov thawj no tau ua rau lub npe hu ua neuroenergetichypothesis, uas pom tau tias qhov mob hnyav zuj zus ntawm cov hlwb hauv hlwb tuaj yeem tsim kev ntxhov siab-tsis muaj zog.

Qhov no txo ​​qis neuronal firing thiab induces ib tug hloov ntawm txoj kev koom nrog physiological APP metabolism rau pathological sawv daws yuav, muaj feem xyuam rau A /tauproduction [139], thaum kawg ua rau AD.

3. Astrocytes raws li Lub Hom Phiaj rau AD Therapeutics

Thaum pib, qhov kev txaus siab ntawm glial hlwb hauv AD tau tshwm sim los ntawm lub luag haujlwm ua los ntawm microglia hlwb hauv lub cev tiv thaiv kab mob [140]. Tom qab ntawd, nws tau pom tseeb tias txhua yam ntawm cov hlwb glial tej zaum yuav koom nrog hauv ob qho tib si etiology thiab kev loj hlob ntawm tus kab mob, raws li cov neeg ua yeeb yam hauv cov ntsiab lus ntawm kev tiv thaiv kab mob thiab cov ntsiab lus tseem ceeb tswj kev koom tes hauv cov txheej txheem molecular thiab cellular hloov hauv AD [141].

Tseeb tiag, cell-type-specifictranscriptomic hloov pauv hauv tib neeg lub hlwb AD tau cuam tshuam nrog cov kab mob sib txawv [142] .Glial hlwb yog cov neeg cell heterogeneous exerting ntau ntau ntawm cov kev ua sib txawv tsim nyog rau kev ua haujlwm ntawm lub hlwb [143]. Glial hlwb feem ntau yog faib ua microglia thiab microglia.

Cov tom kawg muaj cov keeb kwm neural thiab suav nrog astrocytes, oligodendrocytes, thiab NG-2 glia, tseem hu ua synantocytes [144].Microglia yog lub ntsiab tiv thaiv kab mob ntawm lub paj hlwb nrog lub hauv paus chiv keeb uas tsis yog neural. Ua macrophages, lawv ua tiav cov haujlwm tiv thaiv feem ntau [145]. Cov cell no tsis tu ncua tshawb xyuas qhov chaw ib puag ncig nrog lawv cov txheej txheem thiab hloov kho lawv cov morphology thiab kev ua haujlwm nyob ntawm seb lawv xav li cas.

Thaum ua kom muaj zog, microgliaexert chemotactic thiab phagocytic zog, txav mus rau qhov xav tau thiab tshem tawm cov khoom pov tseg, cov khib nyiab ntawm tes, thiab cov kab mob [146]. Ntxiv rau cov kev tiv thaiv tseem ceeb no, microglia siv ntau lwm yam tseem ceeb cuam tshuam txog kev tsim synapse, pruning, thiab ua haujlwm [147-149].

Microglia hlwb qhia ntau yam kev ua kom lub xeev thiab kev nthuav qhia hauv tib neeg lub hlwb AD thiab murine AD qauv [150]. Txoj kev tsom xam ntawm ib leeg-nucleus transcriptomic thwmsim qhia tias cov noob microglial feem ntau cuam tshuam nrog lub cev tiv thaiv kab mob tau qhia txawv ntawm tib neeg lub hlwb AD thiab cov kev tswj hwm [142].

Tsis tas li ntawd, kev hloov pauv hauv TREM2, ib qho ntawm cov cell saum npoo ntawm cov protein tau xaiv thiab nthuav tawm los ntawm microglia hauv lub hlwb, tau cuam tshuam nrog kev pheej hmoo ntau dua peb zaug ntawm kev loj hlob AD [151].Oligodendrocytes los ntawm cov hlwb ua ntej (OPCs) feem ntau nyob hauv thaj chaw ventricular. ntawm lub paj hlwb, los ntawm qhov uas lawv tsiv teb tsaws thaum lub sij hawm txoj kev loj hlob, los ntawm qhov uas lawv ua mature oligodendrocytes.

Cov txheej txheem no pib thaum peb lub hlis thib peb ntawm cev xeeb tub thiab txuas ntxiv mus thoob plaws lub neej [152]. Oligodendrocyte lub luag haujlwm tseem ceeb yog kev tsim ntawm lawv lub cev, qhov tseem ceeb rau kev ua haujlwm zoo ntawm cov paj hlwb ntawm kev ua haujlwm [153].

Hauv qab myelin sheath, nyob rau hauv lub internodal tus kheej qhov chaw, oligodendrocytes tsim kev sib txuas ncaj qha nrog axons ntawm cytoplasmic-nplua nuj myelinic raws, nyob rau hauv uas bidirectional txav ntawm macromolecules tshwm sim ntawm ob lub hlwb [152,154,155].

Impairmentsin myelin tsim thiab kev ua haujlwm muaj feem cuam tshuam rau ntau yam neurodevelopmental andneuropsychiatric disorders [156–160], thiab kev loj hlob ntawm OPCs rau hauv oligodendrocytes isaccelerated los ntawm kev poob ntawm myelin vim raug mob, kev laus, los yog kab mob, nrog rau AD [157] kev tswj hwm hauv tsev CNSA. nyob rau hauv molecular, cellular, lub cev, thiab theem ntawm lub koom haum [161].

Ntau qhov sib txawv ntawm morphologically subtypes ntawm astrocytes tau raug txheeb xyuas uas yuav cuam tshuam rau cov haujlwm tshwj xeeb [162]. Qhov tseeb, lawv yog tam sim no ob leeg hauv cov teeb meem dawb thiab grey.

Astrocytes yog cov khoom tseem ceeb ntawm BBB, yog li tswj kev sib txuas lus ntawm CNS thiab periphery [163]. Lawv tswj CNS microenvironment nyob rau hauv ntau txoj kev, suav nrog los ntawm buffering extracellular ions thiab pH, tswj cov ntshav txaus los ntawm kev tso tawm ntawm vasoactive molecules, thiab clearingreactive oxygen hom (ROS) [164].

Astrocytes yog cov khoom ntawm qhov hu ua gliocrinesystem, tso tawm ib ncig ntawm 200 molecules, feem ntau neurotrophic yam, thiab lub zog substrates, qhov tseem ceeb rau kev saib xyuas ntawm CNS homeostatic functions [165].

Astrocytes exertprimary luag hauj lwm nyob rau hauv synaptic kis tau tus mob thiab cov ntaub ntawv ua los ntawm neural circuits. Nws tau ua pov thawj tias muaj peev xwm ntawm ib qho astrocyte kom nyob rau hauv kev sib cuag nrog ntau cov neuronsand rau modulate synaptic kis tau tus mob los ntawm tuning neurotransmitter theem nyob rau hauv lub synapticcleft [162,163].Keeb kwm muab faib ua OPCs, synantocytes yog stellate hlwb, nrog rau cov txheej txheem loj arborizations uas tshwj xeeb qhia ib tug tshiab. Hom chondroitin sulfate proteoglycan [166].

Lawv pom ob qho tib si hauv cov teeb meem dawb thiab grey thiab cuam tshuam nrog lwm hom glial cell thiab neurons. Synantocytes txuas cov txheej txheem raws li myelin sheaths mus cuag cov paranodesand nodes ntawm Ranvier. Ntxiv mus, lawv tau pom los koom nrog hauv lub txaj txaj txaj txaj muag, tab sis lawv cov haujlwm tshwj xeeb ntawm synapses tseem tsis tau qhia meej [167,168].

Muab cov haujlwm tseem ceeb thiab pleiotropic uas tau tsav los ntawm cov hlwb glial, qhov kev txaus siab rau kev koom tes ntawm cov hlwb no hauv cov kab mob pathophysiology ntawm ntau cov kab mob neurological thiab neuropsychiatric tau loj hlob exponentially hauv ob peb xyoos dhau los [169].

Tsis tas li ntawd, cov xov tooj ntawm tes sib txawv tuaj yeem sib txuas lus thiab cuam tshuam rau ib leeg lub phenotype thiab kev ua haujlwm.Txawm li cas los xij, cov txheej txheem thiab kev cuam tshuam ntawm cov lus sib tham no tsuas yog pib ua kom pom tseeb [124,170,171]. Hauv qab no peb tsom mus rau cov pov thawj txhawb nqa lub luag haujlwm rau impairedastrocyte ua haujlwm hauv AD, thiab cov txiaj ntsig kev kho mob uas muaj peev xwm ua tau raws li aimedat kho lawv tuaj yeem muaj.

Lub luag haujlwm ntawm astrocytes hauv AD yog qhov nyuaj rau kev txiav txim siab, feem ntau yog vim li cas rau ob qho laj thawj: thawj zaug, astrocytes siv ntau ntau ntawm cov haujlwm sib txawv hauv CNS uas tsis yooj yim rau kev sib tw, thiab qhov thib ob, astrocytes teb rau txhua qhov kev cuam tshuam ntawm CNS homeostasis, tshwm sim los ntawm ob qho tib si. kev raug mob los yog kab mob, nrog rau ntau yam kev hloov ntawm cov qauv, transcriptional, thiab ua haujlwm.

Tsis tas li ntawd, cov kev hloov pauv yog tshwj xeeb rau astrocyte localization thiab CNS kev thuam, thiab txawm tias mus rau ntau theem ntawm tus kab mob [125,172–174]. Hais txog AD, cov pov thawj muaj txog tam sim no qhia tias muaj ob qho tib si glial reactivity thiab atrophysince txij thaum pib ntawm AD [97]. Tsis tas li ntawd, astrocytes ze rau amyloid plaquesshow ntau dua transcriptional hloov dua li cov nyob deb ntawm cov plaques [175].

Txhawm rau ua kom cov duab tsis zoo, cov kev tshawb fawb tib neeg tsis ntev los no tau pom tias tom qab AD lub hlwb muaj qhov txo qis ntawm cov neuroprotective astrocytes, uas cuam tshuam nrog glutamate recyclingand synaptic signaling, piv rau kev tswj [142].

Tsis tas li ntawd, kev xav tias astrocytes thaj chaw nyob rau theem kawg ntawm AD tau nce hauv av. Txawm li cas los xij, ob qho tib si reactive thiab asthenicastrocytes ua haujlwm tsis zoo, yog li ua rau muaj qhov sib txawv ntawm cov kab mob los ntawm kev puas hlwb neuronal thiab kev tuag [176].

Yog li ntawd, qhov nyuaj ntawm kev tsim kho tshuaj rau kev tsom mus rau astrocytes nce, txij li cov tshuaj qhia rau hypertrophic astrocytes hauv ib theem AD yuav ua rau muaj kev puas tsuaj rau lwm theem uas astrocytes yog atrophic, thiab vice versa.

Ntxiv mus, modulating astrocytes tuaj yeem cuam tshuam rau kev ua haujlwm ntawm lwm hom glial cell, ntxiv rau cov neurons [177,178], hloov cov kev sib txuas lus ntawm lub hlwb. Lwm qhov kev sib tw tseem ceeb kom kov yeej thaum tsim kev kho mob qhia rau lub hlwb yog qhov tsim nyog rau nws hla BBB. Nws tau tshaj tawm tias tsuas yog 5% ntawm kwv yees li 7000 cov tshuaj tshuaj ntsuam xyuas hauv Cov Ntaub Ntawv Kev Kho Mob Uas Muaj Peev Xwm nkag mus rau CNS dhau BBB [179,180].

Muaj ntau daim ntawv tshaj tawm saib lub luag haujlwm ntawm astrocytes hauv AD, thiab ntau txoj hauv kev tsom mus rau astrocytes tau raug npaj (Daim duab 1). Cov nram qab no tshuaj xyuas ob qho tib si hauv vitro thiab hauv vivo pov thawj uas tau luam tawm nyob rau hauv tsib xyoos dhau los tsom astrocytes pharmacologically hauv cov qauv ntawm AD (Table 1).

For more information:1950477648nn@gmail.com