Epigallocatechin-3-Gallate (EGCG): Kev Pom Zoo Kho Tshiab Rau Neuroprotection, Kev Laus, Thiab Neuroinflammation Rau Hnub Nyoog Niaj Hnub No Part 4

5. Txoj Kev Teeb Meem Teebmeem Teebmeem cuam tshuam hauv Neurodegeneration

Cov yam ntxwv ntawm kev laus hauv lub hlwb yog txo qis neurogenesis, elevatedsynaptic kev puas tsuaj, nce metabolic kev nyuaj siab, kev txawj ntse poob, thiab immunosenescence.

Raws li tib neeg muaj hnub nyoog, lawv lub hlwb kuj muaj hnub nyoog, thiab qhov kev laus no cuam tshuam rau peb txoj kev xav thiab kev nco. Tab sis peb tsis tuaj yeem cia qhov tseeb no ua rau peb poob qis, vim tias muaj ntau yam peb tuaj yeem ua kom qeeb lub hlwb kev laus thaum txhim kho peb lub cim xeeb.

Ua ntej, peb tuaj yeem pab peb lub hlwb kom hluas los ntawm kev tawm dag zog. Kev tawm dag zog lub cev txhawb lub hlwb kev noj qab haus huv los ntawm kev txhim kho cov ntshav ncig thiab ua kom cov pa oxygen thiab cov as-ham. Tsis tas li ntawd, kev tawm dag zog tuaj yeem txo qhov kev ntxhov siab thiab kev ntxhov siab, hais tias muaj kev cuam tshuam tsis zoo rau peb lub hlwb. Yog li ntawd, xyaum qee qhov kev tawm dag zog, xws li taug kev, seev cev, thiab yoga, muaj txiaj ntsig zoo hauv kev tiv thaiv lub hlwb laus.

Qhov thib ob, peb yuav tsum tuav tus cwj pwm zoo siab. Kev zoo siab txhawb kev tso tawm cov neurotransmitters hauv lub hlwb uas tseem ceeb rau kev xav ua haujlwm. Yog li ntawd, peb yuav tsum sib txuas lus nrog cov phooj ywg, koom nrog kev sib raug zoo, sim ua yam tshiab thiab kev ua ub no, thiab lwm yam, kom peb muaj kev zoo siab. Ntxiv rau qhov no, peb tuaj yeem ua rau lub hlwb qeeb qeeb los ntawm kev hloov peb cov zaub mov. Ua kom noj qab nyob zoo uas suav nrog txiv hmab txiv ntoo, zaub, ntses, thiab lwm yam khoom noj uas muaj cov khoom noj muaj txiaj ntsig zoo xws li Omega-3 fatty acids thiab vitamins B, E, thiab C. Cov tshuaj no tiv thaiv cov paj hlwb thiab ua kom cov khoom tsim tawm. neurotransmitters, uas txhim kho kev nco thiab kev xav.

Zuag qhia tag nrho, kev laus ntawm lub hlwb yog qhov tsis tuaj yeem, tab sis muaj cov kauj ruam uas peb tuaj yeem ua kom qeeb cov txheej txheem. Kev tawm dag zog lub cev, tswj tus cwj pwm zoo siab, thiab hloov peb cov zaub mov yog txhua txoj hauv kev zoo kom qeeb lub hlwb laus thiab txhim kho kev nco. Cia peb nquag ntsib lub hlwb laus thiab tsim kom muaj lub neej noj qab nyob zoo thiab zoo nkauj. 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 hauv ntau txoj hauv kev.

Nyem paub 10 txoj hauv kev los txhim kho kev nco

Kev laus kuj tseem cuam tshuam rau kev mob o, nce ntshav-hlwb barrier (BBB) ​​permeability, thiab dysregulated glial cell signaling, cuam tshuam rau mob ntev [101]. Ib txwm glial signaling tswj cov inflammatory teb yog NF-kB, mitogen-activatedprotein kinase (MAPK), thiab phosphoinositide-3-kinase/protein kinase B/mechanistic phiaj ntawm rapamycin (PI3K/AKT/mTOR) txoj kev. Txoj hauv kev NF-κB tau txuas nrog kev ua rau muaj feem cuam tshuam rau kev laus.

NF-κB tuaj yeem txhawb nqa los ntawm ROS, cytokines, inflammatoryagents, loj hlob yam, thiab synaptic kis tau tus mob (feem ntau glutamate). Hauv cov nas, nws tau pom tias microglia stimulation induces ib tug heev conserved transcriptional kos npe nrog aging, characterized los ntawm NF-κB qhia thiab neuronal tuag.

Hauv cov nas, nce NF-κBexpression ua rau muaj kev tsim cov neurodegenerative proinflammatory enzymes: cyclooxygenase 2 (COX-2) thiab inducible nitric oxide synthase (iNOS). Mob ntshav qab zib tau pom tias muaj kev pheej hmoo ntawm AD los ntawm 50% los ntawm kev cuam tshuam A pathology los ntawm NF-κB upregulation thiab kev ywj pheej overexpression ntawm beta-site amyloid precursor protein cleaving enzyme1 (BACE1).

Kev tshawb fawb ntawm primate thiab nas qauv qhia tau hais tias ntshav qab zib thiab rog rog overexpression ntawm NF-κB nyob rau hauv lub hypothalamus los ntawm kev txhawb ib lub voj voog ntawm hypertension, overnutrition, thiab diminished insulin rhiab heev [102].MAPKs muaj xws li serine / threonine kinases tshwm sim los ntawm ntau cov protein kinasesin teb. Extracellular stimuli los ntawm dual phosphorylation ntawm kev txuag threonine andtyrosine residues [103,104].

Txoj hauv kev ntxiv cov teeb liab-tswj kinase (ERK) yog tus neeg ua haujlwm ntawm kev ua haujlwm neuronal. ERK1/2 activation tshwm sim los ntawm ntau yam neurotransmittersand neuropeptides los ntawm induction ntawm ligand-gated ion channels los yog GPCRS; ERK1/2 feem ntau tswj cov cell proliferation thiab yuav tswj cov calcium signaling [103].

Txoj hauv kev c-JunN-terminal kinase (JNK) tau pom los txhawb cov neurodegeneration lossis neuroinflammation los ntawm kev ua rau muaj peev xwm tshem tawm cov stimuli xws li hypoxia, dawb radicals, thiab ROS.

Txoj kev p38 mitogen-activated protein kinase (p38) tuaj yeem txhawb nqa los ntawm ntau yam kev loj hlob (platelet-derived growth factor (PDGF), insulin-likegrowth factor (IGF), thiab vascular endothelial growth factor (VEGF)), pro-inflammatorycytokines, thiab oxidative kev nyuaj siab uas ua rau muaj ntau yam ntawm tes teb xws li mob, apoptosis, cell loj hlob, thiab sib txawv [103].

IL-6 nkoos Janus kinase (JAK), uas ua rau lub teeb liab transducer thiab activator ntawm transcription (STAT), uas provoke theregulation ntawm inflammatory teb.The phosphoinositide-3-kinase/protein kinase B/mechanistic phiaj ntawm rapamycin (PI3K-Akt-mTOR) kev taw qhia txoj hauv kev tswj hwm ntau cov cellular metabolism thiab cov txheej txheem ntawm lub zog, xws li kev loj hlob thiab kev ciaj sia, uas tuaj yeem koom nrog kev tiv thaiv kab mob thiab CNS.

Nws kho cov mob neuronal physiological, xws li kev kawm, nco, thiab kev tiv thaiv kab mob. PI3K yog qhib los ntawm phosphorylation vim muaj kev sib txuas ntawm ntau yam kev loj hlob, xws li epidermal growth factor (EGF) thiab signaling proteins, piv txwv li, (TLR) ligands khi rau receptor tyrosine kinase, uas tso cai rau phosphorylation ntawm phosphatidylinositol 3, 4- bisphosphate (PIP2) rau PI (3,4,5)-triphosphate (PIP3) triphosphate, uas txhawb nqa serine-threonine kinase AKT tswj los ntawm phosphoinositide-dependentkinase 1 (PDK1), uas tuaj yeem ua rau mTOR activation.

Kev tshawb fawb tam sim no tau pom tias muaj qhov sib txawv ntawm txoj hauv kev no rau kev laus thiab, ua ke nrog AD, tuaj yeem hloov pauv AKT thiabmTOR kev ua haujlwm ib txwm muaj txij li ob qho tib si tswj los ntawm oxidative kev ntxhov siab, txo cov khoom noj khoom haus, thiab cov cim tiv thaiv kab mob hauv lub cev.

Ntxiv mus, AD upregulates txoj kev no ua rau inneurodegeneration. Txoj kev taw qhia PI3K-AKT-mTOR txuas nrog kev tswj hwm cov tshuaj insulin (tshwj xeeb yog cerebral insulin), txo qis hauv cov neeg laus ua rau lawv raug rau AD [105,106].

6. Muab Kev Txiav Txim Siab rau qhov tshwm sim ntawm AD: Kev Noj Qab Haus Huv Disparities, poj niam txiv neej, thiab poj niam txiv neej

Kev noj qab haus huv tsis sib xws muaj qhov sib txawv ntawm kev kho mob zoo vim yog kev nyob, haiv neeg / haiv neeg, kev noj qab haus huv ntawm tib neeg, kev ua qias tuaj, kev noj haus, comorbidities, poj niam los txiv neej, thiab keeb kwm kev noj qab haus huv hauv tsev neeg [107]. Lwm qhov tseem ceeb tshaj plaws yog kev paub txog kev cia siab, kev sib txawv ntawm caj ces hauv cov kab mob pathological, thiab qib kev kawm.

Muaj qhov tsis txaus ntseeg ntawm kev tshawb fawb txog kev noj qab haus huv tsis sib xws ntawm cov haiv neeg tsawg, piv txwv li, African Asmeskas (AAs), Latinos, thiab Hispanics, ntsig txog AD [20,108]. Ib tsab xov xwm tshawb fawb los ntawm McDonough [109] qhia txog Huab cua qhov kev xav tau txiav tawm los ntawm Geronimus [110], uas hais tias "kev cuam tshuam ntawm cov uas tau hais los saum toj no kev sib raug zoo, lub cev, thiab kev lag luam uas tau ntsib los ntawm AAs ua rau muaj kev noj qab haus huv tsis zoo thiab kev laus laus," uas tuaj yeem ua tau. siv los ntsuas kev ntxhov siab txog kev ntxhov siab rau cov neeg tsawg ntawm kev noj qab haus huv neurological.

Powell et al. [111] tau soj ntsuam cov kev cuam tshuam hauv zej zog koom nrog hauv AD, kev tshawb xyuas ntu ntu ntawm kev kuaj mob cev xeeb tub los ntawm 447 tus neeg txiav txim siab nyob hauv ib cheeb tsam tsis zoo thaum lub sijhawm tuag.

Lawv pom tias nws muaj feem cuam tshuam nrog kev pheej hmoo siab ntawm Alzheimer's kab mob neuropathology thaum hloov kho hnub nyoog, poj niam txiv neej, thiab xyoo tuag. Lwm qhov kev tshawb fawb cuam tshuam tau ua los ntawm Saadi li al. [112], uas tau qhia tias AAs thiab Hispanics tsis tshua muaj peev xwm (30% txog 40%) kom pom tus kws kho mob sab nraud tshaj li Caucasians, feem.

Tsis tas li ntawd, AAs tau txais kev saib xyuas hauv chav xwm txheej ceev, muaj kev nyob hauv tsev kho mob ntau zaus, thiab them nyiaj ntau dua rau kev saib xyuas neeg mob ntau dua li Caucasians.

Lwm qhov kev tshawb fawb tau piav qhia tias cov kev ntxhov siab hauv zej zog tuaj yeem ua rau muaj kev pheej hmoo rau AD neuropathy [112,113] .Qhov chaw tshawb fawb uas tsis tau txais kev saib xyuas txaus yog qhov sib txawv ntawm poj niam txiv neej thiab poj niam txiv neej pom hauv cov kab mob neurodegenerative.

Cov txiv neej thiab cov poj niam muaj cov txiaj ntsig sib txawv ntawm cov kab mob neurodegenerative tshwm sim los ntawm kev noj qab haus huv, qib kev kawm, noob caj noob ces, thiab qhov sib txawv hormonal [114–116]. Cov kev tshawb fawb tam sim no qhia tau hais tias kev sib deev sib txawv muaj nyob rau hauv kev paub tsis meej txog AD [117,118].

Bloomberg et al. [119] soj ntsuam kev paub txog kev poob qis thiab kev ua tau zoo cuam tshuam nrog kev laus thiab kev kawm thiab pom tias cov poj niam muaj kev nco zoo dua thiab kev nco tsawg dua li cov txiv neej tsis hais txog qib kev kawm. Txawm li cas los xij, kev kawm tau ua qhov tseem ceeb hauv kev xeem kom paub meej, uas cov poj niam uas tau kawm siab dua thiab hauv pawg neeg tom qab tau qhab nia siab dua cov txiv neej. Txawm li cas los xij, tsis muaj qhov sib txawv ntawm kev sib deev hauv kev poob qis [119].

Androgens (testosterone) thiab estrogens tuaj yeem pab tiv thaiv thiab kho cov kab mob neurodegenerative vim lawv muaj ntau yam tshuaj tiv thaiv kab mob, xws li halting proinflammatory cytokine ntau lawm, tiv thaiv oxidative kev nyuaj siab, thiab modulation ntawm A ntau lawm [120,121].

Ntau qhov kev tshawb fawb pom tau tias cov tshuaj estrogen lub paj hlwb tswj kev cuam tshuam ntawm trophic yam hauv lub hlwb ua rau cov ntshav ntws mus rau hauv lub hlwb, txwv tsis pub atrophy ntawm cholinergic neurons, thiab kho BBB glucose transporter expression thiab membrane translocation [122,123].

Kev laus yog lub luag haujlwm ua rau poob ntawm cov tshuaj hormones poj niam txiv neej (androgens thiab estrogens), uas ua rau cov leeg tsis muaj zog, cov leeg tsis muaj zog, txo qis kev ua haujlwm, thiab txo lub neej ntev [124,125].

Cov poj niam Postmenopausal (hnub nyoog 65 xyoos thiab tshaj) muaj kev cuam tshuam rau AD ntau dua li cov txiv neej [122]. Immunological kev sib deev sib txawv muaj nyob rau hauv inmicroglia, raws li qhia nyob rau hauv microglial transcriptomic thiab proteomic kev tshawb fawb uas hloov withage [126,127].

7. Kev Tiv Thaiv Kev Tiv Thaiv Kab Mob Neurodegenerative: Nutraceutical thiab Phytochemical Siv rau Cov Kab Mob Neurodegenerative

Hais txog AD, tsis muaj cov tshuaj tshiab tau pom zoo los ntawm FDA txij li xyoo 2003 thiab tsis muaj kev tso cai kho kab mob hloov kho (DMT), txawm hais tias muaj ntau qhov kev kho mob dav dav [32,33,128]. Xav txog qhov tseeb no, qhov tshwm sim ntawm nutraceuticals tau ua rau muaj peev xwm tshiab ntawm kev tswj tus kab mob no.

Nutraceuticals yog ib lub ntsiab lus dav dav uas suav nrog ntau cov khoom lag luam uas tshwm sim los ntawm kev lag luam zaub mov, tshuaj ntsuab thiab kev noj haus ntxiv kev lag luam, tshuaj, thiab hybrid agribusiness / khoom noj khoom haus lag luam uas tej zaum yuav muaj peev xwm kho tau tus kab mob [96].

Nutraceuticals tau txais txiaj ntsig zoo heev rau lawv cov keeb kwm ntev ntawm kev siv thiab muab lwm txoj hauv kev rau cov tshuaj tam sim no hauv khw [96]. Nutraceuticals tau pom tias muaj anti-inflammatory, antioxidative, thiab anti-aging zog.

Cov txheej txheem tiv thaiv kab mob / tshuaj tiv thaiv kab mob tshwm sim los ntawm nutraceuticals yog raws li hauv qab no: (a) cuam tshuam NFκB ua kom, (b) inhibitoverexpression ntawm proinflammatory cytokines, (c) downregulation ntawm overexpression ofcalcium / Calmodulin (CAM) thiab enzymes, (d) thaiv enzymatic kev ua ntawm COX-2 thiab iNOS, (e) ntes ROS enzymatic ntau lawm, thiab (f) nce ROS scavenging [129].

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