Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery For Neurodegenerative Diseases Part 2
Jun 25, 2024
3. Protein misfolding nyob rau hauv cov kab mob Neurodegenerative
Kev hloov pauv ntawm cov proteins los ntawm lawv lub xeev mus rau misfolded aggregates yog txuam nrog thiab xav tias yuav ua rau qee qhov NDs, suav nrog AD thiab PD [133]. Cov misfolding, aggregation, thiab deposition ntawm cov proteins tshwj xeeb yog cov yam ntxwv tseem ceeb ntawm feem ntau progressiveNDs [21,134].
Protein yog ib qho ntawm cov khoom noj tseem ceeb rau tib neeg lub cev. Nws yog lub hauv paus ntsiab lus uas tsim lub cev lub hlwb thiab tseem yog ib qho ntawm cov khoom tseem ceeb hauv paus rau ntau yam kev ua haujlwm ntawm lub cev ntawm tib neeg lub cev. Protein kuj tseem ua lub luag haujlwm tseem ceeb hauv kev txhim kho kev nco.
Ua ntej tshaj plaws, cov protein tuaj yeem pab peb txhim kho peb txoj kev xav thiab yog li txhim kho peb lub cim xeeb, vim tias cov protein yog qhov tseem ceeb ntawm cov paj hlwb. Neurons yog lub hauv paus units uas tsim lub hlwb thiab lub paj hlwb. Kev ua haujlwm nco thiab xa cov ntaub ntawv hauv lub hlwb xav tau kev sib txuas lus thiab kev sib koom tes ntawm cov neurons. Yog li, kev noj cov protein kom txaus tuaj yeem pab peb tiv thaiv lub paj hlwb thiab txhim kho kev sib cuam tshuam ntawm cov paj hlwb thiab cov paj hlwb hauv lub hlwb, yog li txhim kho lub peev xwm kawm, nco, thiab xav.
Qhov thib ob, cov protein tuaj yeem pab peb tswj peb txoj kev xav, txo kev ntxhov siab thiab kev ntxhov siab, thiab txhawb kev txhim kho kev nco. Cov kev tshawb fawb tau pom tias cov neeg uas tsis muaj protein ntau feem ntau pom cov tsos mob ntawm kev ntxhov siab xws li kev chim siab, ntxhov siab, thiab chim siab vim tias cov protein yog lub hauv paus rau kev sib txuas ntawm kev xav-tswj tshuaj. Nws tuaj yeem pab tib neeg lub cev tsim cov tshuaj neurotransmitters xws li dopamine, yog li tswj kev xav. Thaum peb cov kev xav tau ruaj khov thiab so kom txaus, lub hlwb cov ntaub ntawv muaj peev xwm ua kom tiav, thiab peb lub cim xeeb kuj yuav txhim kho raws li.
Hauv cov ntsiab lus, cov protein yog ib qho tseem ceeb uas tsim nyog rau tib neeg lub cev, thiab nws kuj ua lub luag haujlwm tsis tuaj yeem hloov pauv hauv kev txhim kho kev nco. Yog li ntawd, peb yuav tsum tsom ntsoov rau kev noj cov protein ntau hauv peb cov zaub mov noj txhua hnub, txhim kho kev ua haujlwm ntawm ntau yam tseem ceeb hauv lub cev, txhim kho kev xav thiab kev xav, thiab ua kom peb ua tau zoo thiab zoo dua hauv kev kawm thiab kev ua haujlwm. 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 kab mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidation thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv kev noj qab haus huv. 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 tam sim no txhawm rau txhim kho lub hlwb ua haujlwm
A , tau, -syn, TDP-43, yos hav zoov, lossis prion protein (PrP) tsuas yog ob peb yam piv txwv ntawm cov kab mob tshwj xeeb uas tuaj yeem sib sau ua ke thiab pab txhawb rau cov kab mob NDs (Daim duab 2).
Cov misfolded protein aggregates ua rau cellular toxicity thiab nws thiaj li ua rau cell tuag nyob rau hauv neurodegenerative pathologies. Nyob rau hauv txhua rooj plaub, cov txheej txheem sib sau ua lub luag haujlwm tseem ceeb hauv kev kis tus kab mob los ntawm kev poob ntawm cov protein ua haujlwm (raws li qhov tshwm sim ntawm kev sib sau nws tus kheej) lossis rau cov toxicity ntawm soluble aggregates [17,22].
Muab hais tias NDs pib los ntawm txoj kev sib sau ua ke, nrog rau kev sib sau ua ke sib koom ua ke, nws tsis yog qhov xav tsis thoob tias cov aggregates no ua rau cov cellular puas los ntawm cov txheej txheem zoo sib xws.
Txawm li cas los xij, qhov sib txawv tseem ceeb ntawm cov misfolded proteins tshwm sim rau qhov chaw ntawm cov khoom sib sau, txawm tias nyob rau hauv-los yog extracellular, thiab lawv cov concentration, uas nyob ntawm ntau yam, nrog rau kev ruaj ntseg ntawm cov fibrils [93].
Nws yog qhov paub zoo tias qhov tsis sib xws, sib sau ua ke, thiab sib sau ua ke ntawm cov protein ua rau muaj kev puas tsuaj rau cov neurons uas cov proteins khaws cia, ua rau cov txheej txheem neurodegeneration [135].
Ib qho protein tshwj xeeb tuaj yeem quav mus rau hauv qhov kev hloov pauv ruaj khov, uas feem ntau ua rau nws sib sau ua ke thiab sib sau ua ke hauv cov ntaub so ntswg li fibrillar deposits [136].
Cov pov thawj ntxiv qhia tau hais tias kev sib sau ntawm amyloid fibrils yog nrog los ntawm kev hloov pauv hauv cov protein sib sau ua ke. Piv txwv li, cov 'natively unfolded' polypeptidesA thiab -syn, muaj ib qho piv txwv ntawm random-coil qauv hauv lawv cov soluble, nativestate [24].
Txawm li cas los xij, nyob rau hauv cov txheej txheem fibrillogenesis (Daim duab 3), lawv cov qauv hloov mus rau hauv daim ntawv sib haum, qhia tias -daim ntawv tsim tsav cov txheej txheem amyloid sib dhos.
Tsis tas li ntawd, nyob rau hauv vitro thwmsim qhia tias cov misfolded proteins yooj yim formcross- qauv nrog ib tug aggregation kinetics profile uas feem ntau qhia ib sigmoidalcurve qhov twg cov proteins sib sau ua ke rau hauv oligomers (lag theem) ua ntej fibril elongation (loj theem) thiab ib tug toj siab qhov twg cov fibrils thiab dawb. monomers nyob rau hauv equilibrium (saturation theem) [137,138].
Tseeb, amyloid fibril tsim yog ib tug complex, multiphase txheej txheem uas muaj peb theem: nucleation los yog lag theem, elongation los yog theem loj hlob, thiab saturationphase.
Lub lag luam theem pib nrog cov monomers tab tom kho cov txheej txheem rov qab thiab nws tus kheej sib dhos rau hauv dimers, trimers, thiab / lossis oligomers. Nyob rau theem kev loj hlob, lub oligomericnucleus ua raws li tus qauv rau cov monomers hauv kev daws teeb meem thiab ua tiav los ntawm fibril elongation, pab los ntawm fragmentation, theem nrab nucleation, thiab fibril conjoining.
Thaum kawg, cov fibrilformation nce mus txog qhov sib npaug hauv lub sijhawm saturation nrog cov fibrils paub tab thiab txo qis ntawm hom monomeric [138].
Qhov tseem ceeb, Stanley Prusiner qhov kev tshawb pom tias PrP tuaj yeem ua tsis zoo rau hauv cov kab mob pathological uas encodes cov ntaub ntawv muaj peev xwm ntawm ob qho tib si propagating thiab inducing mob hnyav neuropathology tau pab cuam tshuam rau kev nkag siab lwm yamNDs [139,140].
Thaum muaj pov thawj ntxiv tias lwm cov NDs, tshwj xeeb tshaj yog AD (A andtau) thiab PD (-syn), muaj tsawg kawg yog qee yam ntawm tib yam khoom xws li misfolded PrP, ntau NDs nrog cov protein misfolding tivthaiv tam sim no hu ua 'prion-zoo li'. [141, 142].
Txawm hais tias cov protein sib txawv tau koom nrog hauv txhua ND, cov txheej txheem ntawm cov protein misfolding thiab kev sib sau ua ke zoo sib xws. Misfolded proteins yog pauv ntawm cov hlwb, ua dab tsi yog hu ua 'pathological noob' [136].
Cov kev tshawb fawb soj ntsuam qhia tias cov rooj sib txoos no los ntawm cov prion-zoo li cov noob sib sau ua ke ntawm cov misfoldedproteins tshwj xeeb uas tsim thiab tsim kom muaj cov kab mob hauv lub cev thiab / lossis cov kab mob extracellular ntawm txhua qhov teeb meem [135,143,144]. Lub prion paradigm tau tshwm sim ua ib lub hauv paus unifyingmolecular rau pathogenesis ntawm ntau NDs [145].
Lub prion paradigm tuav tau hais tias lub misfolding thiab seeded aggregation ntawm tej yam proteins yog ib qho tseem ceeb ua rau ntawm tej yam mob. Qhov kev tshawb pom no muaj qhov cuam tshuam loj heev rau kev nkag siab txog cov txheej txheem koom nrog hauv kev pib thiab kev loj hlob ntawm NDs, nrog rau kev tsim kho tshiab thiab cov tswv yim kuaj mob.
Cov kws tshawb fawb tam sim no tsom mus rau kev txhim kho kev kho mob rau cov protein misfolding disorders uas siv cov tswv yim sib txawv. Cov no muaj xws li inhibiting zus tau tej cov proteins uas muaj feem xyuam rau misfolding, inhibiting lub aggregation ntawm misfolded proteins, tshem tawm thiab tiv thaiv kev sib kis ntawm aggregated misfolded proteins, thiab manipulating cellular systems kom txo tau cov tshuaj lom los ntawm misfolded proteins [19].
Txij li thaum protein misfolding thiab kev sib sau ua ke yog qhov ua rau muaj ntau NDs, ntau cov kev tshawb fawb tau tshuaj xyuas lub peev xwm ntawm kev tsom mus rau cov txheej txheem fibrillization ntawm amyloid proteins los tawm tsam neurodegeneration.
Ib qho array ntawm cov tebchaw tau raug txheeb xyuas tias muaj peev xwm inhibitors lossis modulators ntawm protein misfolding thiab aggregation.Qhov tseem ceeb, feem ntau ntawm cov lus cog tseg uas tau txheeb xyuas lub hom phiaj misfolded A thiab -syn; Cov molecules zoo li khi rau oligomers thiab cov aggregates loj xws li asamyloid plaques [146,147].
Cov tebchaw no tuaj yeem muab faib ua peb hom: cov tshuaj tiv thaiv kab mob, peptide inhibitors, thiab cov tshuaj tiv thaiv me me xws li NPs [132].Thaum kawg, muab ntau cov ntaub ntawv pov thawj uas txhawb nqa cov protein misfolding raws li qhov tshwm sim thiab cov txheej txheem pathological hauv NDs, nws tau pom zoo. hais tias ib qho kev kho mob rau cov kab mob kho tsis tau zoo no tuaj yeem ua tau [24].
Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias lub peev xwm ntawm EGCG tawm tsam ntau NDs txhawb qhov muaj peev xwm ntawm kev txhim kho cov tshuaj siv tshuaj sib txawv rau NDs sib txawv. Nyob rau hauv xyoo tsis ntev los no, lub luag hauj lwm ntawm natural polyphenol EGCGaginst protein misfolding thiab aggregation tau dav kawm.
Muaj ntau yam pov thawj tam sim no muaj los txhawb lub peev xwm ntawm EGCG los tiv thaiv fibrillization thiab muaj peev xwm ua rau lub cev tsis sib haum xeeb ntawm cov proteins uas tsis sib xws (A , tau, thiab -syn) [148–151].
3.1. Misfolded A hauv AD
A yog ib qho misfolded peptide koom nrog hauv AD pathogenesis, thiab cov quav hniav tsim los ntawm aggregated A peptide nta prominently hauv AD pathology; Yog li, feem ntau cov tshuaj uas tau sim rau AD nyob rau ob lub xyoo dhau los tau tsom rau A peptide [50,66].
A peptides yog 39–42-cov peptides ntev-ntev pom nyob rau hauv cov plaques senile ntawm AD cov neeg mob lub hlwb [61]. Cov peptides no yog proteolytic fragments generated los ntawm cov metabolism ntawm transmembraneamyloid precursor protein (APP), uas ces nws tus kheej-aggregate nyob rau hauv aqueous tov, mus los ntawm soluble thiab feem ntau unstructured monomers rau insoluble txiav txim fibrils.
Sai li A aggregates mus rau hauv fibrils sab nraum lub cell, nws yuav tiv taus proteolytic cleavage [61,152] .Lub cleavage ntawm APP los ntawm ib tug complex tsev neeg ntawm enzymes (-secretases thiab -secretases) tso tawm A peptides raws li feem ntau unstructured monomers [152]. Muab qhov hydrophobicity ntawm thawj tus qauv, A tuaj yeem muab faib ua plaub thaj tsam: ob lub hydrophobic ones thiab ob hydrophilic ones.
Lub 16 thawj N-terminal residues tsim ib tus Tsov tus tw hydrophilic, thaum ob thaj chaw hydrophobic yog suav nrog hauv nruab nrab L17-A21 feem thiab C-terminus A30-V40 / A42, uas yog cais los ntawm lub hauv paus hydrophilic cheeb tsam E22-G29.
Ob lub cheeb tsam A hydrophobic nthuav tawm cov qauv kev xav thib ob rau -structures.Cov cheeb tsam no tau hloov pauv hloov pauv thiab tuaj yeem hloov pauv mus rau hauv aairpin.
Nws tau raug pom tias A monomers hauv kev daws tau txais kev hloov pauv ntawm cov plaub hau zoo li qub, qhov seem D23 rau K30 yog ncaj qha koom nrog hauv kev tsim cov plaub hau [152].Raws li tau hais yav dhau los, txawm tias muaj teeb meem ntawm cov plaques, ib lub cev loj ntawm cov pov thawj implicates soluble oligomeric. A raws li feem ntau neurotoxic molecular hom [70,153,154].
Cov misfolding thiab extracellular aggregation ntawm A peptides tau lees paub tias yog lub ntsiab ua rau AD kev loj hlob, ua rau tsim cov tshuaj lom A oligomers thiab deposition ntawm -amyloid plaques nyob rau hauv lub hlwb [61]. Nws tau raug pom tias oligomeric A hom tuaj yeem sawv cev rau lub hom phiaj lom neeg siv tau [66,155,156].
3.2. Misfolded -Syn hauv PD
Cov protein -syn feem ntau nyob hauv thaj chaw synaptic, qhov chaw uas nws cuam tshuam nrog ntau tus neeg koom tes xws li monoamine transporters, cytoskeletal Cheebtsam, lipidmembranes, chaperones, thiab synaptic vesicle (SV)-kwv yees proteins [157].
Lub -syn ismonomeric thiab tsis meej pem hauv nws daim ntawv physiological, txawm hais tias qee qhov kev tshawb fawb sib cav tias nws siv lub helical tetramer hauv vivo [158-160]. Ntxiv rau kev sib sau ua ke ntawm intracellular aggregation ntawm misfolded -syn raug txuas rau PD, nws tau cuam tshuam rau lwm cov NDs xws li AD, ntau qhov system atrophy (MSA), thiab dementiawith Lewy lub cev.
Tsis tas li ntawd, ib pawg kab mob hu ua synucleinopathies yog tus cwj pwm los ntawm kev sib sau ntawm kev suav nrog nplua nuj nyob hauv cov protein -syn uas tuaj yeem tshwm sim tom qab lub neej [161,162]. Nws tau xav tias ntau hom aggregated hom (oligomers, protofibrils, fibrils, thiab lwm yam) yog tsim thaum lub sij hawm tus txheej txheem ntawm -syn aggregation nyob rau hauv cov synucleinopathies thiab hais tias tsawg kawg ib co tej zaum yuav neurotoxic thiab ua rau neurodegeneration [163].
Yog li ntawd, kev tsom mus rau cov neuronal tsub zuj zuj ntawm -syn yog txaus siab raws li ib txoj kev muaj peev xwm haltor ncua kev loj hlob ntawm PD thiab lwm yam synucleinopathies [164].
Lub 140-amino acid -syn yog 14 kDa neuronal protein encoded los ntawm SNCA geneon human chromosome 4 [165]. Nws thawj cov amino acid ib ntus tuaj yeem muab faib ua peb qhov tseem ceeb: N-terminal domain (1-60), lub hauv paus domain (61-95), thiab C-terminal domain (96-140).
N-terminal domain, uas muaj ntau qhov kev pom zoo ua ntu zus (KTKEGV) thiab muaj qhov ua tau zoo-helical, yog tus cwj pwm los ntawm anamphipathic lysine-nplua nuj amino terminus, uas ua lub luag haujlwm tseem ceeb hauv kev hloov kho nws cov kev cuam tshuam nrog daim nyias nyias thiab kev tsis sib haum xeeb, acidic carboxy- davhlau ya nyob twg. Tus Tsov tus tw tau cuam tshuam rau kev tswj hwm nws qhov chaw nyob hauv nuclear thiab kev cuam tshuam nrog cov hlau, cov khoom me me, thiab cov proteins.
Lub hauv paus cheeb tsam ntawm -syn muaj ib tug heev hydrophobicmotif hu ua cov uas tsis yog-amyloid-tivthaiv ntawm AD amyloid plaques (NAC), uas yog koom nyob rau hauv -syn aggregation thaum tau txais cov qauv-daim ntawv. NAC cheeb tsam yog qhov tseem ceeb rau -syn aggregation.
C-terminal domain yog enriched nrog negativelycharged thiab proline residues, muab kev yooj yim rau cov polypeptide [166,167] .Vim lub NAC cheeb tsam ntawm -syn confers ib siab propensity rau cov protein mus misfold, itforms -sheet amyloid assemblies, kuj hu ua fibrils, nyob rau hauv Txawm li cas los xij, kev sib dhos -syn rau hauv amyloid fibrils yog dynamic, thiab lub hav zoov ntawm intermediate oligomeric hom tau kawm ntau heev [164].
Zoo ib yam li oligomeric A , -syn oligomers ua rau muaj kev cuam tshuam neurotoxic ntau dua li cov rooj sib txoos loj ntawm fibrillar, inferring tias lawv yuav yog hom kab mob tseem ceeb [168].
Cov tshuaj lom nruab nrab ntawm qhov kev xav tau tsim los ntawm qhov kev pom no, qhia tias cov tshuaj lom oligomers cuam tshuam kev ncaj ncees ntawm daim nyias nyias ntawm amyloid pore tsim, thaum cov khoom siv fibrillar tsuas yog ib qho los ntawm kev ua kom detoxification.
Qhov kev pom no tau txais kev txhawb nqa los ntawm qhov tseeb tias fibril-muaj Lewy lub cev feem ntau pom muaj nyob rau hauv noj qab haus huv dopaminergic neurons [169–171].
4. EGCG rau Kev Kho Mob Neurodegenerative Diseases
Nyob rau hauv lub teeb ntawm lub peev xwm loj ntawm kev siv tshuaj yej ntsuab hauv ND kev kho mob, tshuaj yej ntsuab catechinshave tau kawm dav, suav nrog hauv vitro thiab hauv vivo kev tshawb fawb thiab kev sim tshuaj [16,117].Qhov kev kho mob muaj peev xwm ntawm EGCG, qhov loj bioactive compound ntawm ntsuab tshuaj yej, yog tam sim no paub zoo hauv ND tshawb fawb [10]. Tshaj li 20 xyoo dhau los, EGCG tau pom tias muaj kev cuam tshuam txog kev ntxhov siab thiab txhim kho AD- thiab PD-zoo li phenotypes sib txawv hauv vitro thiab hauv vivomodels (Tables 2 thiab 3).
4.1. Cov ntaub ntawv pov thawj los ntawm In Vitro Neurotoxicity Models
Nyob rau xyoo 1990, kev tshawb fawb nrog A-induced neurotoxicity qauv qhia tau hais tias qhov tshwm sim ntawm A 1-42 ua rau neurotoxicity thiab muaj protein ntau oxidation thiab, vim li ntawd, oxidative stress [220–222].
Lub neurotoxicity ntawm A protein yog kho los ntawm oxygen dawb radicals thiab tuaj yeem txo qis los ntawm cov tshuaj tua kab mob antioxidant thiab cov dawb radical scavengers. Theattenuation ntawm oxidative kev nyuaj siab los ntawm antioxidant tebchaw, yog li ntawd, yog ib tug muaj peev xwm kho lub tswv yim rau kev kho AD.
Thaum ntxov xyoo 2000s, cov khoom muaj zog antioxidant ntawm cov tshuaj yej ntsuab polyphenol EGCG tau tshawb xyuas hauv A -induced neurotoxicity modelusing cultured hippocampal neurons, nrog rau cov txiaj ntsig tau qhia tias EGCG muaj kev tiv thaiv tiv thaiv A-induced neuronal apoptosis los ntawm scavenging reactive oxygen hom. ntawm thawj daim ntawv qhia txog cov txiaj ntsig ntawm EGCG rau kev tiv thaiv AD [172].
Tom qab ntawd, cov txheej txheem molecular hauv qab cov nyhuv neuroprotective ntawm EGCG hauv A -induced neurotoxicity qauv tau tshawb xyuas nrog kev tsom mus rau cellularmetabolism ntawm txo glutathione nrog cov khoom antioxidant. Cov txiaj ntsig tau qhia tias EGCG kev kho mob tiv thaiv lub cellular glutathione pas dej ntawm kev nthuav qhia ntawm -glutamylcysteine ligase [176].
Oxidative stress kuj tau pom tias yuav ua rau BACE-1 protein upregulation inneuronal hlwb, uas yog tus nqi-txheej enzyme nyob rau hauv APP ua thiab A tiam, thiab raws li ib tug kho lub hom phiaj rau AD [223,224]. Txawm hais tias raug tus kab mob A 1-42 toneuronal kab lis kev cai nce BACE-1 cov protein ntau, EGCG kev kho mob txo qis A -induced zus tau tej cov radical oxygen thiab -sheet qauv tsim [174].
Thaum ntxov xyoo 2010, nws tau paub tias EGCG inhibits A thiab -syn fibrillogenesis incell-free assays; Cov kws tshawb fawb tau tshawb xyuas seb EGCG puas tuaj yeem hloov kho qhov tsis sib haum A thiab -syn aggregates hauv cov qauv cell [148].
Qhov kev tshawb fawb no tau pom tias EGCG tuaj yeem txo cov cellular toxicity ntawm mature A thiab -syn fibrils los ntawm kev hloov kho lawv cov qauv. TheEGCG-mediated remodeling ntawm -sheet-nplua nuj amyloid qauv ua rau cov tsos ntawm cov me me amorphous protein aggregates uas tsis muaj tshuaj lom rau cov tsiaj nyeg [148].In 2017, kev ua haujlwm ntawm -syn-transduced PC12 hlwb tau ua los tshawb xyuas qhov kev tiv thaiv ntawm EGCG, muab pov thawj tias EGCG tuaj yeem tiv thaiv cov cell tiv thaiv -syn-induced kev puas tsuaj los ntawm inhibiting lub overexpression thiab fibrillation ntawm -syn hauv hlwb [151].
Ib txoj kev tshawb fawb tsis ntev los no tau tshaj tawm tias EGCG tuaj yeem cuam tshuam nrog Cu(II)-induced fibrillationof -syn thiab tiv thaiv cell viability. Cov kws tshawb fawb tau pom tias EGCG inhibits qhov tsim ntawm Cu(II)-induced reactive oxygen hom (ROS), ua rau txo qis overexpression thiab fibrillation ntawm -syn hauv hlwb. Tsis tas li ntawd, kev sib xyaw ua ke ntawm Cu thiab EGCG tau nthuav tawm cov kev tiv thaiv zoo tshaj li EGCG ib leeg. Ntawm no, nws tsim nyog sau cia tias Cu (II) yog anoxidant uas tseem ua rau fibrillation thiab protein aggregation [183].
Tseem muaj cov ntaub ntawv pov thawj ntawm cov teebmeem neuroprotective ntawm EGCG nyob rau hauv neurotoxicity qauv ntawm PD Parkinsonian neurotoxins suav nrog cov tebchaw xws li 6-hydroxydopamine(6-OHDA), 1-methyl-4-phenyl{4 }},2,3,6-tetrahydropyridine (MPTP), rotenone (ROT), thiab paraquat. EGCG tau ua pov thawj zoo tshaj plaws neuronal tiv thaiv paraquat, 6-OHDA, thiab MPP + neurotoxicity, txawm tias tsis tawm tsam ROT [173,175,178,180,181].
Hauv kev ntsuam xyuas ntawm cov teebmeem neuroprotective ntawm EGCG ntawm ROT-kho dissociatedmesencephalic kab lis kev cai thiab organotypic striatal kab lis kev cai, EGCG ib nrab counteracted cov teebmeem ntawm ROT nyob rau hauv striatal daim kab lis kev cai los ntawm kev txo cov nitric oxide (NO) tab sis tsis dissociate hlwb tawm tsam ROT toxicity [178] .
Txawm hais tias txoj kev tshawb fawb tom kawg tsis tau qhia tias EGCG tiv thaiv ROT-induced neurotoxicity hauv cov qauv ntawm tes, nws tsis ntev los no tau tshaj tawm tias EGCG muaj cov nyhuv neuroprotective hauv vivo ntawm ROT-induced PDmodels [206,207]. Ua ke, cov txiaj ntsig tau los ntawm cov qauv hauv vitro neurotoxicity txhawb kev xav tias EGCG tuaj yeem siv los ua tus neeg saib xyuas neuroprotective los kho NDs.
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