Kev Tshawb Fawb Txog Kev Tshawb Fawb Txog Kev Tshawb Fawb Ntawm Cov Tshuaj Suav Tshuaj Ntsuab Tshuaj Extracts Regulating Ferroptosis Yog li txhim kho cov tsos mob ntawm Alzheimer's Disease

Abstract: Alzheimer's Disease (AD)yog ib hom kab mob neurodegenerative hauv cov neeg laus. Nws cov xwm txheej kho mob tshwm sim yog qhov ua rau nco tsis taus. Ferroptosis, nce raws li kev tshawb fawb tshiab ntawm AD's biologicalmechanism nyob rau hauv xyoo tas los no, feem ntau yog kev tshawb fawb txog hlau-dependent programmed cell tuag. Ntau cov pov thawj tau pom tias AD muaj feem cuam tshuam nrog ferroptosis hauv lub hlwb. Txawm li cas los xij, qhov tseeb mechanism ntawm lub luag haujlwm ferroptosis tau ua si hauv AD tseem tsis paub meej. Ib qho ntawm cov txiaj ntsig kev tshawb fawb nrov tshaj plaws qhia tau hais tias AD tuaj yeem raug cuam tshuam los ntawm cov hlau metabolism tsis zoo, lipidperoxidation, thiab cov amino acid metabolism, yog li cuam tshuam rau kev tso tawm ntawm cov hlau ions hauv lub hlwb. Txog tam sim no, qee cov tshuaj muaj txiaj ntsig zoo ntawm cov tshuaj suav tshuaj suav tshuaj raws li kev kho rau AD tau kawm hauv qhov tob, xws li Rhodiola rosea, polygalaroot, ginkgo biloba, Cistanche, Poria cocos, thiab lwm yam. Cov tshuaj suav tshuaj suav tshuaj no tau pom muaj txiaj ntsig zoo hauv kev kho ADusing. tsom rau ferroptosis. Hauv cov ntsiab lus no, qhov kev tshuaj xyuas no piav qhia txog cov metabolism hauv cov hlau hauv lub hlwb, thiab cov yam ntxwv ntawm ferroptosis, thiab tsom mus rau cov txheej txheem metabolic ntawm ferroptosis. Lub caij no, qhov kev tshuaj xyuas no kuj tham txog kev sib txuas ntawm ferroptosis thiab AD. Tsis tas li ntawd, nws teev cov kev sib xyaw ua ke hauv cov tshuaj suav tshuaj suav tshuaj uas tuaj yeem txhim kho AD los ntawminhibiting ferroptosis, yog li muab cov ntaub ntawv siv rau kev txhim kho thiab kev tshawb fawb offerroptosis inhibitors yav tom ntej.

Ntsiab lus: Kab mob Alzheimer;Cov tshuaj suav tshuaj; Ferroptosis; Mechanism of action; Review

HIGH-QUALITY CISTANCHE HERBA RAUALZHEIMER'S DISEASE (AD)Kev kho mob

Alzheimer tus kab mob (AD)yog ib hom kab mob neurodegenerative hauv cov neeg laus, nrog rau kev nco tsis zoo raws li nws qhov kev kho mob tshwm sim. Xyoo 1906, tus kws tshawb fawb German Alois Alzheimer thawj zaug tau tshaj tawm ib rooj plaub ntawm tus poj niam laus cov neeg mob uas muaj kev mob dementia ntev. Tom qab kev tuag, qhov kev txiav txim siab ntawm lub hlwb tau qhia txog kev hloov pauv ntawm lub hlwb xws li lub hlwb atrophy, neurofibrillary tangles (NFTs), thiab senile plaques (SP) [1]. Daim ntawv ntsuam xyuas kab mob kis tshiab tshaj tawm qhia tias muaj txog 15.07 lab tus neeg mob dementia hnub nyoog tshaj 60 xyoo hauv Suav teb, suav nrog 9.83 lab tus neeg mob AD [2]. Nws kwv yees hais tias los ntawm 2050, lub ntiaj teb no prevalence ntawm dementia yuav nce 2 zaug [3]. Ob tug yam ntxwv tseem ceeb ntawm AD yog extracellular SP nyob rau ntawm amyloid protein (A) thiab intracellular NFTs muaj li ntawm phosphorylated microtubule-txuas protein ntau (Tau). Txij li tsis muaj qhov tseeb qhov tseeb ntawm qhov laj thawj thiab cov txheej txheem tshwj xeeb ntawm AD, feem ntau cov kev sim tshuaj tsom rau A thiab Tau cov proteins, tab sis cov txiaj ntsig kev tshawb fawb tam sim no tsis zoo. Yog li ntawd, nws yog ib qho tsim nyog yuav tsum tshawb nrhiav cov lus qhia tshiab kom meej meej txog lub peev xwm ntawm AD.

Hlau tsub zuj zujtuaj yeem ua rauferroptosis, ib tug tshiab nrhiav tauiron-dependent programmed cell tuag, uas yog morphologically, biochemically, thiab genetically txawv ntawm apoptosis, ntau hom necrosis, thiab autophagy. Nws yog feem ntau tshwm sim los ntawm kev txo qis cell ntim thiab nce mitochondrial membrane ntom, tsis muaj cov yam ntxwv ntawm necrosis thiab apoptosis [4]. Cov kev tshawb fawb soj ntsuam ntsig txog tau pom tias qhov ntev ntev ntawm cov hlau raug mob tuaj yeem cuam tshuam nrog cov hlau homeostasis thiab kev faib tawm, nce oxidative kev nyuaj siab, ua rau mitochondrial tsis ua hauj lwm thiab DNA oxidative puas tsuaj, thiab induce neuronal poob, yog li ua rau muaj kev pheej hmoo ntawm AD [5]. Tsis tas li ntawd, qee qhov kev tshawb fawb tau pom tias cov proteins uas cuam tshuam txog ferroptosis tau nthuav tawm ntau dua nyob rau hauv cov ntaub so ntswg hippocampal ntawm AD nas [6], xws li glutathione peroxidase 4 (GPX4), cov neeg nqa khoom solute tsev neeg 7 tus tswv cuab 11 (SLC7A11), acetyl-CoA synthetase ntev. -chain family 4 (ACSL4), and phosphatidylethanolamine binding protein 1 (PEBP1). Cov pov thawj saum toj no qhia rau qee qhov uas ferroptosis tau koom nrog hauv kev tsim ntawm AD. Nyob rau hauv xyoo tas los no, cov tshuaj tiv thaiv neuroprotective uas tsom rau txoj hauv kev ferroptosis los tswj AD kuj maj mam tsim, tshwj xeeb tshaj yog kev tshawb fawb ntawm cov khoom xyaw ntuj hauv cov tshuaj suav tshuaj hauv kev tswj ferroptosis hauv AD. Tsab ntawv xov xwm no tshuaj xyuas cov kev tshawb fawb txog kev ua tiav ntawm ferroptosis mechanism hauv AD thiab cov khoom xyaw ntuj suav tshuaj suav tshuaj uas tswj ferroptosis, los muab kev pab rau yav tom ntej kev tshawb fawb tshuaj thiab kev txhim kho cov txheej txheem ferroptosis.

HIGH-QUALITY CISTANCHE HERBA RAUALZHEIMER'S DISEASE (AD)Kev kho mob

1 Kev tshawb nrhiav cov ntaub ntawv zoo

PubMed thiab CNKI databases tau tshawb xyuas los ntawm lub computer, thiab lub sijhawm tshawb nrhiav tau teem sijhawm txij Lub Ib Hlis 2018 txog rau Lub Rau Hli 2024. Cov lus tshawb hauv Suav suav nrog "hlau homeostasis", "ferroptosis", "hlau metabolism", "hlau overload", thiab "Alzheimer's disease. ", thiab cov lus Askiv tshawb fawb suav nrog "hlau homeostasis", "hlau tuag", "hlau metabolism", "hlau overload", thiab "Alzheimer's disease".

Cov txheej txheem suav nrog: Cov ntaub ntawv uas muaj kev sib raug zoo thiab kev ua haujlwm ntawm cov hlau homeostasis, ferroptosis, hlau metabolism, hlau overload, thiab lwm yam, thiab Alzheimer's disease. Cov txheej txheem cais tawm: Cov ntaub ntawv uas tsis cuam tshuam nrog lub ntsiab lus ntawm tsab xov xwm no, tsis tau tshaj tawm, thiab cov ntawv qub tsis tuaj yeem muab tau.

2 Hlau thiab nws cov metabolism hauv hlwb hlwb

Cov hlau hloov pauv ntau tshaj plaws nyob rau hauv lub hlwb yog hlau, uas yog dav nyob rau hauv ntau yam cellular txheej txheem ［7］, xws li mitochondrial muaj nuj nqi, neuronal myelination, thiab cov synthesis thiab metabolism ntawm neurotransmitters. Yog li ntawd, hlau metabolism yuav tsum tau nruj me ntsis tswj. Ob qho tib si hlau tsis muaj peev xwm thiab overload tuaj yeem ua rau lub hlwb tsis ua haujlwm [8]. Piv txwv li, lub hlwb tsis muaj hlau nyob hauv cov me nyuam mos thiab cov me nyuam yaus tuaj yeem ua rau muaj kev puas siab puas ntsws thiab kev puas siab puas ntsws psychomotor. Yog tias cov hlau tso ntau dhau rau hauv lub hlwb laus, nws muaj feem cuam tshuam nrog qhov tshwm sim ntawm ntau yam kab mob neurodegenerative, suav nrog AD. Iron homeostasis nyob rau theem cellular nyob ntawm tsis yog tsuas yog nyob rau hauv lub cev qhia ntawm hlau nqus (influx) proteins ntawm daim nyias nyias, tab sis kuj nyob rau hauv lub physiological qhia ntawm hlau tso (efflux) proteins ntawm daim nyias nyias. Ntau qhov kev tshawb fawb yav dhau los tau pom tias cov hlwb endothelial ntawm cov ntshav-cerebrospinal fluid barrier (BBB) ​​yog cov chaw tswj hwm rau lub hlwb hlau nqus. Kev nqus hlau hauv lub hlwb suav nrog kev hloov pauv / hloov pauv receptor (Tf / TfR1), ferritin hnyav saw (FTH1), lactoferrin-lactoferrin receptor (Lf/LfR), thiab secretory p97-glycosylphosphatidylinositol (GPI) anchored p97 (PI-SP97/GPI) P97) txoj kev [9].

Lub xub ntiag ntawm TfR1 thiab divalent hlau ion transporter 1 (DMT1) nyob rau hauv daim nyias nyias ntawm cov neurons, oligodendrocytes, microglia, thiab astrocytes qhia tias lawv muaj peev xwm coj mus rau transferrin-bound hlau (Tf-Fe) los yog non-transferrin-bound hlau (NTBI) ntawm txoj kev TfR1 / DMT1 lossis DMT1, ua raws li cov hlau tso tawm los ntawm ferroportin 1 (Fpn1) / ceruloplasmin (CP) thiab / lossis Fpn1 / heparin (Heph) txoj kev [10]. Hlau dysregulation yog txheej txheem tseem ceeb hauv AD, thiab ferroptosis yog ib qho txheej txheem tshiab txuas rau lub hlwb hlau dysregulation rau neuronal tuag.

3 Ferroptosis thiab nws cov txheej txheem metabolic

3.1 Ferroptosis

Ferroptosis yog ib qho kev tswj hwm cell tuag hom uas yog hlau-nyob thiab tsav los ntawm lipid peroxidation. Cov kev tshawb fawb yav dhau los tau pom tias cov ntaub so ntswg ntawm cov neeg mob AD feem ntau pom cov kev hloov pauv pathological raws li ferroptosis [11]. Nyob rau tib lub sijhawm, nce ferritin thiab hlau tuaj yeem pom hauv cov ntaub so ntswg ntawm tib neeg AD [12]. Tsis tas li ntawd, tag nrho cov qib hlau nyob rau hauv cov kab mob qog nqaij hlav hauv tib neeg lub hlwb muaj kev cuam tshuam zoo nrog tus nqi ntawm kev txawj ntse poob tom qab kuaj mob AD [13]. Cov no ua pov thawj tias muaj kev sib raug zoo ntawm ferroptosis thiab AD. Cov yam ntxwv ntawm ferroptosis muaj xws li cov kev hloov pauv hauv cell morphology (mitochondrial condensation, ploj ntawm cristae, nce ob chav membrane ntom), hlau-dependent aggregation ntawm reactive oxygen hom (ROS) thiab lipid peroxides, poob ntawm glutathione (GSH), inactivation ntawm GPX4. , thiab cov txheej txheem tshwj xeeb ntawm kev tswj cov noob [14].

3.2 Metabolic mechanism ntawm ferroptosis

Txij li thaum cov txheej txheem metabolic ntawm ferroptosis yog qhov nyuaj hauv tsev thiab txawv teb chaws, thiab ntau yam tseem tsis tau paub meej, cov hauv qab no feem ntau piav qhia txog kev koom tes ntawm ferroptosis hauv AD txheej txheem los ntawm peb yam: hlau metabolism tsis meej, lipid peroxidation, thiab amino acid metabolism. .

3.2.1 Iron metabolism tsis meej: Kev saib xyuas ntawm cov hlau homeostasis yuav tsum muaj kev ua haujlwm ntawm cov hlau metabolism, suav nrog kev khaws cia, kev siv, thiab tshem tawm cov hlau. Hlau dysregulation yog ib qho ntawm cov cim ntawm ferroptosis. Cov kev tshawb fawb cuam tshuam tau pom tias cov hlau ntau dhau tuaj yeem ua rau ferroptosis hauv vivo thiab hauv vitro thaum muaj cov txheej txheem pathological [15]. Ua kom ferritin degradation los yog inhibiting ferritin qhia yuav ua rau kom cov hlau hauv lub cev (LIP) thiab ua kom cov hlwb rhiab heev rau ferroptosis. Piv txwv li, cov lus qhia theem ntawm hepcidin thiab ferroportin tau txo qis hauv hippocampus ntawm AD hlwb [16]. Tsis tas li ntawd, tsis tshua muaj kev qhia ntawm Nedd4 tsev neeg interacting protein 1 (Ndfip1) tej zaum yuav muaj kev koom tes nyob rau hauv lub pathogenesis ntawm AD los ntawm kev txo cov degradation ntawm DMT1 thiab nce hlau tsub zuj zuj [17]. Nuclear factor E2-related factor 2 (NRF2) tswj qhov rhiab heev ntawm cov hlwb rau ferroptosis los ntawm inhibiting qhov qhia ntawm transferrin receptor 1, cuam tshuam rau cov hlau metabolism [18]. Ib txoj kev tshawb nrhiav pom tias hlau tuaj yeem txhawb txoj kev loj hlob ntawm AD los ntawm kev ua rau microglial ferroptosis thiab neuronal tuag [19]. Hlau aggregation yog kho tsis tau tsuas yog los ntawm Tau phosphorylation tab sis kuj los ntawm kev hloov ntawm hlau ntawm divalent thiab trivalent xeev. Hyperphosphorylated Tau aggregates nrog trivalent hlau ions los tsim cov tshuaj insoluble, ua rau tsim NFTs hauv AD hlwb [20]. Tsis tas li ntawd, kev cuam tshuam ntawm cov hlau metabolism ua rau muaj qhov txawv txav ntawm intracellular tsis ruaj tsis khov hlau, uas tom qab ntawd ua rau Fenton cov tshuaj tiv thaiv thiab Haber-Weiss cov tshuaj tiv thaiv, tsim cov dawb radicals, thiab activates ferroptosis [21]. Nyob rau hauv luv luv, nce hlau nqus los yog txo cov hlau cia yuav cuam tshuam qhov rhiab heev ntawm cov hlwb rau ferroptosis. 3.2.2 Lipid peroxidation: Kev sib sau ntau ntawm lipid peroxides mus rau theem tuag yog lwm tus yam ntxwv ntawm ferroptosis. Lipid peroxidation metabolites qhia kev sib koom ua ke nrog amyloid plaques thiab muaj feem cuam tshuam nrog AD kev nce qib [22].

Kev sib sau ntawm lipid ROS thiab txo qis cortical GSH cov ntsiab lus tau pom hauv AD pathology [23]. Lipid peroxide tsub zuj zuj yog lub hauv paus ntawm ferroptosis. Lipid metabolomics qhia tau hais tias polyunsaturated fatty acids xws li arachidonic acid (AA) thiab adrenic acid (AdA) nyob rau hauv tus txheej txheem ntawm ferroptosis yog cov feem ntau raug lipids rau oxidation cov tshuaj tiv thaiv thiab yog yooj yim tswj los ntawm peb synthases: ACSL4, lysophosphatidyl transferase 3 (LPCAT3) thiab LPCAT3. lipoxygenase (LOX). Thaum lub sij hawm lipid peroxidation, arachidonic acid-CoA thiab adrenoyl-CoA yog catalyzed, thiab thaum kawg, AA/AdA-PE-OOH yog tsim nyob rau hauv lub catalysis ntawm LOX, los yog tshuaj lom thib ob cov khoom yog tsim los ntawm decomposition, xws li 4-hydroxy -2-nonenal (4-HNE) lossis malondialdehyde (MDA). Cov tshuaj tiv thaiv oxidation tsis tu ncua ua rau tsis muaj kev puas tsuaj rau cov qauv thiab kev ua haujlwm ntawm cov cell membrane thiab plasma membrane, ua rau tsim cov pores ntawm cell membrane, thiab tom qab ntawd pib ferroptosis ntawm neurons, ua rau kev puas tsuaj rau lub paj hlwb [17]. Cov kev sim tau pom tias khob tawm los yog inhibiting cov saum toj no peb synthases tuaj yeem inhibit qhov tshwm sim thiab kev loj hlob ntawm ferroptosis [24-26].

3.2.3 Amino acid metabolism: Amino acid metabolism ua lub luag haujlwm tseem ceeb hauv ferroptosis. Ob tus neeg tseem ceeb cuam tshuam rau ferroptosis yog cystine / glutamate antiporter (system Xc-) thiab GPX4. Cov tsev neeg thauj khoom solute SLC7A11 yog ib qho tseem ceeb ntawm qhov system Xc-.

GPX4 yog lub hom phiaj tseem ceeb rau kev ua rau ferroptosis thiab cov enzyme tseem ceeb hauv cov kab mob antioxidant GSH [27]. Lub depletion ntawm cellular GSH thiab inactivation ntawm GPX4 kho LPO thiab koom nyob rau hauv ferroptosis, thiab yuav ua tau raws li ib tug tseem ceeb regulator ntawm ferroptosis [28]. Cov kev tshawb fawb tau pom tias GSH qib hauv hippocampus thiab frontal cortex yuav dhau los ua biomarker rau kwv yees AD [13]. Tsis tas li ntawd, cov kev sim cuam tshuam tau pom tias qhov kev qhia ntawm GPX4 thiab SLC7A11, qhov tseem ceeb ntawm ferroptosis, hauv AD nas raug txo, thiab qib ntawm TfR tau nce, uas tau txhim kho tom qab Fer-1 kho [29], qhia. uas tswj hwm qib GSH ib txwm muaj thiab GPX4 muaj nuj nqi hauv cov hlwb tuaj yeem cuam tshuam qhov tshwm sim ntawm ferroptosis. Ferroptosis tuaj yeem raug ntxias los ntawm qee qhov me me, suav nrog Erasin thiab RSL3, tshwj xeeb tshaj yog RSL3, uas tuaj yeem cuam tshuam ncaj qha GPX4 kev ua haujlwm, thaum Erastin tsis ncaj qha txo cov biosynthesis ntawm GSH thiab GPX4 los ntawm inhibiting system Xc- [17]. Txawm hais tias nws tsis ncaj los yog ncaj qha inhibition ntawm GPX4, nws yuav ua rau tsis muaj peev xwm tshem tawm lipid peroxides, tsub zuj zuj ntawm lipid peroxides hauv hlwb, thiab ua rau ferroptosis.