Lub luag hauj lwm ntawm cov vitamins nyob rau hauv Neurodegenerative Disease: Ib Qhov Hloov Kho 2

Kev soj ntsuam kuaj pom tau tias ascorbic acid (200 mg) zoo heev rau cov neeg laus PD. Hauv qhov kev sim tshuaj no, cov kws sau ntawv tau hais tias ascorbic acid txhim kho qhov nqus ntawm levodopa (100 mg levodopa thiab 10 mg carbidopa) hauv qhov tseem ceeb hauv cov neeg mob PD.

Nyob rau hauv xyoo tas los no, muaj kev txaus siab rau kev sib raug zoo ntawm ascorbic acid thiab nco. Ascorbic acid, tseem hu ua vitamin C, yog ib qho tseem ceeb vitamin rau tib neeg lub cev. Nws muaj ntau yam haujlwm tseem ceeb hauv lub cev, xws li redox, antioxidant, kev tu tawv nqaij, thiab kev tiv thaiv qhov muag. Raws li kev tshawb fawb, ascorbic acid kuj zoo sib xws rau kev txhim kho kev nco.

Ua ntej ntawm tag nrho cov, ascorbic acid yog ib tug muaj zog antioxidant uas yuav tshem tawm dawb radicals nyob rau hauv lub cev thiab txo oxidative kev puas tsuaj rau lub hlwb, yog li tiv thaiv kev noj qab haus huv ntawm lub cev. Dawb radicals yog los ntawm cov khoom ntawm cov cell metabolism. Thaum cov hlwb sau ntau cov dawb radicals ntau dhau lawm, lawv yuav ua rau lawv cov kev ua haujlwm lom neeg tsis zoo thiab ua rau kev laus thiab kab mob. Yog li ntawd, tswj kom txaus ascorbic acid kom tsawg tuaj yeem txo qhov cuam tshuam ntawm cov dawb radicals ntawm lub cev, pab tswj lub cev noj qab haus huv, thiab yog li txhim kho kev nco.

Thib ob, ascorbic acid tuaj yeem txhawb nqa cov haujlwm ntawm cov receptors hauv lub hlwb, ua rau lub hlwb nco thiab kev kawm muaj peev xwm ua kom nrawm dua. Kev tshawb fawb qhia tau hais tias kev haus ascorbic acid txaus hauv cov zaub mov lossis tshuaj tuaj yeem ntxiv dag zog rau lub hlwb kev ua haujlwm, yog li pab txhim kho tib neeg kev nco. Ascorbic acid kuj tseem tuaj yeem txhawb kev tsim cov tshuaj hormones thiab txhim kho kev ruaj ntseg ntawm lub paj hlwb, yog li txhawb kev loj hlob, kev loj hlob thiab kho cov neurons, thiab txhim kho kev xav thiab kev txawj ntse.

Hauv cov ntsiab lus, ascorbic acid yeej muaj feem cuam tshuam nrog tib neeg kev nco. Yog li, peb yuav tsum ua tib zoo saib xyuas kev noj zaub mov kom txaus ntawm ascorbic acid. Piv txwv li, noj txiv hmab txiv ntoo thiab zaub ntau ntxiv hauv ascorbic acid tuaj yeem pab txhim kho lub cev tiv thaiv kab mob, tiv thaiv lub hlwb kev noj qab haus huv, thiab txhim kho kev nco. Nws tuaj yeem pom tau tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola muaj cov tshuaj antioxidant, tiv thaiv kev 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. ntawm lub paj hlwb. Tsis tas li ntawd, Cistanche deserticola Nws kuj 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 thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv kev loj hlob ntawm kev paub tsis meej thiab cov kab mob neurodegenerative.

Nyem paub txhim kho lub sij hawm luv luv

Yog li ntawd, kev kho combinatorial ntawm ascorbic acid nrog levodopa yuav tau txais txiaj ntsig zoo dua li kev kho mob ntawm ib leeg [80]. Txawm li cas los xij, tseem muaj kev tsis sib haum xeeb hauv kev siv VitC rau kev kho mob ntawm PD, thiab kev tshawb fawb ntxiv yog xav tau [21].Cov kws tshawb fawb kuj tau qhia txog kev sib txuas ntawm vitamin D (VitD) thiab PD, thiab txawm tias muaj kev siv zog, nws tseem tsis tau meej meej. yog tias qhov tsis txaus hauv VitD yog lub luag haujlwm rau PD lossis qhov tshwm sim ntawm PD [81].

Cutaneous theem ntawm VitD yog ncaj qha cuam tshuam rau tshav ntuj raug [82,83], thiab ultraviolet raug rau cov qib ntawm VitD hauv peb lub cev [84,85]. Cov pob txha ntom yog ncaj qha nrog cov concentration ntawm VitD thiab yog li kev ruaj ntseg postural [86]; Txawm li cas los xij, lub luag haujlwm ntawm VitD hauv lub hlwb tsis nkag siab tsawg. Calcitriol (1,25- dihydroxy vitamin D3) yog cov tshuaj tiv thaiv kab mob metabolite thiab feem ntau kawm daim ntawv ntawm VitD [87].

Piv nrog rau cov hnub nyoog sib tw noj qab haus huv, PD cov neeg mob muaj qhov qis dua ntawm calcitriol hauv lawv cov ntshav plasma, uas tej zaum yuav cuam tshuam rau pob txha noj qab haus huv thiab kev pheej hmoo ntawm pob txha [88,89]. Interestingly, tus receptor ofcalcitriol kuj qhia nyob rau hauv CNS [90]. Yog li, VitD kho nws cov teebmeem hauv PD los ntawm nws daim ntawv nquag, calcitriol, thiab cov receptors cuam tshuam tam sim no hauv CNS [86,91].

One txoj kev tshawb fawb qhia txog kev sib hloov pauv thiab kev ua haujlwm lom ntawm vitamin D hauv PD [92]. Lwm txoj kev tshawb fawb kuj qhia txog qhov toxicity ntawm VitD uas yog lub luag haujlwm rau cov tsos mob rov qab los ntawm Parkinsonism [93].Regrettably, ib qho kev tshuaj ntsuam xyuas meta tsis ntev los no pom muaj ob peb txoj kev tshawb fawb tsom rau vitamin D supplementation hauv PD kev kho mob. Txoj kev tshawb no qhia txog kev sib cuam tshuam ntawm VitD theem thiab kev pheej hmoo thiab qhov hnyav ntawm PD hauv 2866 PD cov neeg mob [94]. Muaj cov lus teb tsis pub dhau ntawm VitDsupplementation (Ntau dua lossis sib npaug li 400 IU / hnub) hauv cov neeg mob PD thaum ntxov, thiab qhov kev lees paub no ntxiv kev tshawb fawb ntxiv rau nws cov peev xwm kho tau [95].

Yog li ntawd, kev tshawb fawb ntau ntxiv ntawm cov neeg mob PD thaum ntxov thiab lig yog xav tau los teeb pom kev sib txuas ntawm VitD thiab PD ntxiv.Vitamin E (VitE) yog ib qho tshuaj tiv thaiv antioxidant uas muaj nyob hauv cov zaub, thiab nws muaj ntau yam kev siv kho mob [96]. Los ntawm nruab nrab -1990s, lub luag haujlwm ntawm VitE tau pom muaj ntau yam kab mob hauv lub paj hlwb suav nrog PD [97]. Zoo ib yam li lwm cov vitamins, VitE muaj kev sib txuas nrog PD [97].

Cov txiaj ntsig tau los ntawm kev tshawb fawb tsis ntev los no tau pom tias qhov cuam tshuam ntawmVitE yog hnub nyoog- thiab kev sib deev- ywj pheej thiab pom tias muaj kev sib cuam tshuam ntawm VitE intake thiab PD tshwm sim [97]. Yog li ntawd, kev noj zaub mov nplua nuj nyob hauv VitE tuaj yeem txo qhov kev pheej hmoo cuam tshuam nrog PD [98,99].Qhov kev loj hlob ntawm PD yuav raug tswj los ntawm cov koob tshuaj alpha-tocopherol thiab ascorbate raws li qhia los ntawm kev tshawb nrhiav.

Kev sim tshuaj ntxiv nyob rau theem dav dua yuav xav tau kom paub meej txog kev tiv thaiv kev tiv thaiv ntawm alpha-tocopherol thiab ascorbate [100]. Raws li pom los ntawm kev sim tshuaj, kev siv tshuaj ntau vitamin E (2000 IU vitamin E hauv ib hnub) kev kho mob txhim kho cov concentration hauv cov kua cerebrospinal (CSF) ntawm tus neeg mob PD thaum ntxov. HighCSF thiab lub hlwb siab ntawm alpha-tocopherol qhia txog kev tiv thaiv ntawm cov neeg mob PD [101]. Ib txoj kev tshawb fawb kuj qhia tau hais tias tsis muaj kev sib raug zoo ntawm cov ntshav ntshav VitE andrisk ntawm PD [102].

Lwm txoj kev tshawb fawb pom zoo txhua hnub multivitamin supplementation uas yuav tsum muaj tsawg kawg yog 30 IU ntawm alpha-tocopherol es tsis txhob ntawm 400 IU ntawm alpha-tocopherol nyob rau hauv cov tib neeg cuam tshuam. Qhov kev sib xyaw ua ke no tau pom qhov kev kho tau zoo dua hauv cov neeg mob PD [103]. Ib txoj hauv kev multivitamin los ntawm kev siv vitamin E, vitamin C, thiab carotenoidsis tsis muaj txiaj ntsig hauv kev txo qis PD. Hloov chaw, kev noj zaub mov muaj vitamin supplementation nplua nuj nyob rau hauv VitEshows txhim kho kev muaj peev xwm los txo qhov kev pheej hmoo PD. Ib koob tshuaj ntau heev yuav ua rau poob hauv kev kho mob ntawm Vitamin E [104].

Yog li ntawd, yuav tsum tau saib xyuas, thiab yuav tsum muaj kev tshawb fawb dav dav los ua pov thawj qhov kev kho mob ntawm VitE. Acase tsab ntawv ceeb toom ntawm tus neeg mob laus PD qhia txog kev kho kom zoo ntawm cov tshuaj multivitaminmultimineral supplementation nrog Ginkgo biloba [105]. Ib txoj kev tshawb fawb pej xeem loj yog qhov tsim nyog kom paub meej tias tib yam.

4.2. Vitamin Raws li Tsiaj Studies hauv Parkinson's Disease

Cov cellular retinol-binding protein pom nyob rau hauv cov ntshav-hlwb barrier (BBB) ​​tso cai rau lub hlwb nkag tau yooj yim rau VitA thiab nws cov derivatives [106]. Hauv CNS, lub hom phiaj tseem ceeb ntawm RAaction yog nigrostriatal dopaminergic system [107,108]. RA-receptor heterodimers khi rau RA- teb cov ntsiab lus hauv cheeb tsam txhawb nqa thiab tsav cov kev hloov pauv ntawm thedopamine 2 receptor gene.

Xws li, RA receptor knockout nas tau txo qis kev qhia ntawm D2 dopamine receptors [60]. Yog li, RA receptor zoo tswj cov kev tswj hwm ntawm homeostatic ntawm nigrostriatal dopaminergic system raws li kev txhawb nqa los ntawm ntau cov pov thawj [108-111]. Yog li, kev tshawb nrhiav ntxiv rau hauv kev koom ua ke ntawm VitAin yav tom ntej PD kev kho mob tuaj yeem ua pov thawj muaj txiaj ntsig. Ib txoj kev tshawb fawb tsis ntev los no tau qhia tias tsis muaj teebmeem ntawm qhov ncauj ntxiv ntawm retinol hauv 6-hydroxydopamine intoxicated Wistar ratmodel [112].

RA receptor raws li txoj kev kho mob yuav muaj txiaj ntsig zoo hauv kev tiv thaiv kev loj hlob ntawm PD thiab qhia txog cov txheej txheem ntawm kev ua tom qab nws [113]. Lycopene yog ib qho tseem ceeb carotenoid uas tseem nthuav tawm nws cov txiaj ntsig hauv MPTP-induced Parkinsonianmouse qauv. Cov kev kho mob lycopene thim rov qab lub cev tsis zoo, oxidative kev nyuaj siab, neurochemical abnormalities, thiab apoptosis. Lycopene qhia txog kev tiv thaiv apoptotic thiab antioxidative zog hauv PD nas qauv [114]. Lycopene tseem tiv thaiv kev paub txog kev poob qis hauv rotenone-induced PD qauv [115].

Vitamin C (VitC), uas tib neeg tsis tuaj yeem tsim los ntawm qhov tsis muaj enzyme L-gulonolactone oxidase, muaj ntau yam txiaj ntsig kev noj qab haus huv nrog rau qhov tseem ceeb antioxidantactivities [116]. Piv txwv li, kev kho mob nrog VitC txo qis PD-zoo li phenotype ofdopaminergic neuron degeneration thiab locomotor deficits hauv UCH-L1 noob knockdownDrosophila PD qauv (Daim duab 2) [117].

Tsis ntev los no, ib txoj kev tshawb fawb tau tshawb fawb txog cov tshuaj tiv thaiv kab mob ntawm VitC siv tus qauv flydown no. Cov kws sau ntawv tau tawm tswv yim tias rau kev kho PD, VitC koob tshuaj tiv thaiv kev ua haujlwm yuav tsum tsis txhob raug ignored vim tias muaj ntau ntawm VitC muaj kev cuam tshuam tsis zoo rau tus cwj pwm thiab kev ua haujlwm [118]. Ascorbic acid (100 mg / kg) kev tswj hwm ua ntej 20 min ntawm MPTP intoxication pom muaj kev tiv thaiv los ntawm nws cov tshuaj tiv thaiv kab mob hauv BALB / c PD qauv (Daim duab 2) [119]. microglialactivity thiab tiv thaiv kev tuag ntawm dopaminergic neurons (Daim duab 2) [120].

Hauv cov qauv nas hemiparkin-sonian, VitD tiv thaiv kev tuag ntawm dopaminergic neurons los ntawm inhibiting oxidativestress thiab neuroinflammation [121].Cov tsos mob zoo li PD thiab cov kab mob cuam tshuam txog mitochondrial abnormalities thiab synaptic impairment nyob rau hauv ib tug PD knockdown qauv tau zoo txhim kho los ntawmVitE supplementation [9] ]. Kev noj haus ntev ntawm VitE (500 mg / kg-kev noj haus) txo qis kev tuag ntawm dopaminergic neurons hauv substantia nigra ntawm zitter mutant nas qauv ntawm PD [122]. 

Txawm li cas los xij, ntau tus kws tshawb fawb tau pom qhov sib txawv ntawm qhov kev tshawb pom txog kev noj zaub mov noj ntawm VitE rau kev kho mob ntawm PD [123]. Tocotrienols (T3s) yog cov tswv cuab paub zoo ntawm VitEfamily uas tseem muaj peev xwm tiv thaiv kab mob neuroprotective los ntawm lawv cov tshuaj tiv thaiv oxidative [124].Biochemical thiab kev coj tus cwj pwm pov thawj tau pom tias PD kev loj hlob ntawm kev txhaj tshuaj los ntawm intrastriatal 6-OHDA tau ameliorated los ntawm VitE kev kho mob hauv PD nas qauv [125].Ib yam li ntawd, kev coj tus cwj pwm, neurochemical, thiab biochemical kev tshawb fawb tau ua pov thawj tias VitE tau txais txiaj ntsig therotenone-induced nas qauv [126].

Cov pov thawj histochemical thiab biochemical kuj tau qhia tias qhov rov ua haujlwm ntawm cov tshuaj vitamin E (24 IU / kg, im) muaj cov cuab yeej tiv thaiv neuroprotective tseem ceeb hauv cov nas thaum ntxov PD raug ntxias los ntawm unilateral intrastriatal 6-hydroxydopamine (12.5 microg / 5 microl) [127 ]. Alpha-tocopherol kuj tau nthuav tawm cov kev ua haujlwm zoo li neuroprotective hauv unilateral 6-OHDA qauv thiab tej zaum yuav raug siv los ua cov tshuaj PD [128].

Cov txiaj ntsig tau los ntawm kev tshawb fawb pom tau tias kev sib xyaw ua ke ntawm ntau dua ntawm Coenzyme Q10 (CoQ10) (600 mg / kg / hnub) nrog levodopa (10 mg / kg / hnub) tiv thaiv cov neeg mob los ntawm neurodegeneration hauv rotenone-induced nas qauv ntawm Parkinsonism. Raws li piv rau cov koob tshuaj qis qis ntawm CoQ10 (200 mg / kg / hnub) nrog levodopa (10 mg / kg / hnub). Cov koob tshuaj ntau dua ntawm CoQ10 nrog levodopa txhim kho qhov txawv txav hauv cov khoom siv hluav taws xob thauj khoom thiab nthuav tawm cov haujlwm tiv thaiv apoptotic. Striatal dopamine qib tau rov qab zoo dua los ntawm qhov kev kho mob no [129].

4.3. Cov vitamins hauv Cell-Based Parkinson's Disease

Ib txoj kev tshawb fawb pluripotent qia-cell-raws li qhia tau hais tias RA- yog qhov zoo tshaj plaws ntawm thiab RA receptors hauv kev tsim cov striatopallidal-zoo li neurons hauv PD los ntawm kev cuam tshuam cov dopamine2 receptor gene [130]. Niacin (VitB3) qhia tau hais tias muaj zog tiv thaiv kev ua haujlwm los ntawm nws cov receptor GPR109A los ntawm inhibiting lub nuclear translocation ntawm NF-κB hauv lipopolysaccharide (LPS)-induced RAW264.7 cell qauv ntawm PD. Qhov no nuclear inhibition ntawm NF-κB tiv thaiv kev txhim kho ntawm proinflammatory cytokines thiab cuam tshuam neurodegeneration hauv tus qauv PD [131].

NADH yog cov nquag coenzyme ntawm VitB3. NADH ua rau kom muaj kev tso tawm ntawm dopamine los ntawm cov pob zeb striatal ntawm 350 microM concentration hauv vitro. Tsis muaj kev cuam tshuam ntawm NADH (10 lossis 100 mg / kg) hauv vivo. Rau kev sib txuas thiab rov tsim dua tshiab ntawm tetrahydrobiopterin, NADH xav tau. Tsis tas li ntawd, tetrahydrobiopterin xav tau los ua kom muaj Tyrosine hydroxylase, tus nqi txwv enzyme hauv kev sib txuas ntawm dopamine.

Ib txoj kev tshawb fawb yuav tsum tau lees paub qhov kev tshawb pom hauv vitro hauv tus qauv hauv vivo [132]. Hauv cov qauv acellular ntawm PD, cov ciaj sia taus thiab lub zog ua haujlwm tau txhim kho tau zoo los ntawm Nicotinamide mononucleotide (NMN). Nyob rau hauv tib neeg neuroblastoma cell kab SK-N-SH, ascorbic acid (200 microM) coj mus rau kev nthuav qhia (peb-fold) ntawm tyrosine hydroxylase (TH) tom qab 5 hnub ntawm kev kho mob.

Yog li ntawd, dopamine synthesis tau nce ntxiv los ntawm kev nthuav qhia ntawm TH. Yog li ntawd, ascorbic acid tej zaum yuav siv nyob rau hauv thaum ntxov PD raws li apotential anti-Parkinsonian tus neeg sawv cev [133]. Hauv cov qauv ntawm tes, ascorbic acid kuj nthuav tawm nws cov peev xwm kho mob tiv thaiv levodopa-induced neurotoxicity [134]. MN ameliorated the process of apoptosis in this cellular model [135].

Tsis tas li ntawd, cov kev tshawb fawb tau pom tias 1,25-dihydroxyvitamin D3 tau pom muaj zog tiv thaiv kab mob thiab cov kab mob neuroprotective, thiab txo cov neurotoxin-induced microglial activation thiab kev qhia ntawm proinflammatory cytokines hauv cov qauv kev sim ntawm cov kab mob sib kis-mediated neurodegenerative (Daim duab 63 1) [13] ].Nyob rau hauv ib lub cellular PD qauv, T3s nthuav tawm cytoprotective kev ua los ntawm estrogenreceptor-activated -PI3K/Akt txoj kev [124].

Hauv kev xaus, ntau ntawm tes-, tsiaj-, thiab tib neeg-raws li kev tshawb fawb tau pom tias cov vitamin muaj txiaj ntsig zoo hauv kev tiv thaiv thiab / lossis kev kho mob ntawm PD vim lawv cov tshuaj tiv thaiv oxidant thiab lwm yam kev ua haujlwm lom neeg xws li kev tswj cov noob caj noob ces.Txawm li cas los xij, qee cov kev tshawb fawb tsis pom zoo [ 21]. Tshwj xeeb, qee qhov kev tshawb fawb kuj qhia tau tias tsis muaj kev cuam tshuam txog kev kho mob ntawm cov vitamins. Tsis tas li ntawd, koob tshuaj yog qhov tseem ceeb heev uas txiav txim siab qhov ua tau zoo ntawm cov vitamins hauv PD. Yog li ntawd, kev tshawb fawb ntxiv yog tsim nyog los qhia meej txog kev siv cov vitamin supplementation inPD therapeutics.

5. Cov vitamins hauv Alzheimer's Disease

Thoob plaws ntiaj teb, Alzheimer's disease (AD) yog thawj qhov tshwm sim ntawm txhua yam kab mob neurodegenerative [105]. Hauv cov neeg laus, AD yog qhov feem ntau ua rau dementia [138]. Cov tsos mob ntawm AD pib nrog kev paub tsis meej, uas txuas ntxiv mus rau dementia [139]. AD neuropathology suav nrog kev nce zuj zus ntawm cov neurons, tsim cov amyloid (A) plaques, thiab neurofibrillary tangles (NFT) ntawm hyperphosphorylated tau protein [140,141].

Yog li ntawd, kev soj ntsuam tom qab mortem ntawm AD cov neeg mob hlwb qhia txog qhov txo qhov loj ntawm lub paj hlwb cortex thiab abnormaldeposits sab hauv thiab ib ncig ntawm neurons [138]. Zoo ib yam li lwm cov kab mob neurodegenerative, ib qho ntawm cov ua rau lub luag hauj lwm rau kev loj hlob neurodegeneration hauv AD yog oxidativestress [142]. Cov ntaub ntawv pov thawj tau pom tias cov tshuaj tiv thaiv oxidative ntawm cov vitamins yuav muaj txiaj ntsig zoo hauv kev kho AD. Xws li, cov vitamins tau siv los ua adjuvantsin AD kho [6,143].

5.1. Vitamins Raws li Clinical Studies nyob rau hauv Alzheimer's Disease

Hauv kev kho AD, nicotinamide tuaj yeem siv los ua kev kho mob ntxiv vim nws yog apotent inhibitor ntawm Poly (ADP-ribose) polymerase 1 [144]. Ntau daim ntawv pov thawj tau pom zoo tias piv rau cov tib neeg noj qab haus huv uas tsis muaj kev paub txog kev ua haujlwm tsis zoo, cov neeg mob AD pom tias txo qis ntawm VitA, VitB, thiab VitC hauv cov ntshav ntshav [145]. Meta-analyticstudies tau pom tias txo cov ntshav ntshav ntawm VitA, VitB [6,9,21], VitC, VitD, VitE, thiab VitK hauv AD cov neeg mob [146,147]. Ntxiv mus, txo qib ntawm VitA, VitC, thiab VitE tau pom cov neeg mob indementia piv rau kev noj qab haus huv tswj [148,149].

Interestingly, ib tug cross-sectionaland prospective txoj kev tshawb no qhia hais tias ib tug ua ke ntawm VitC thiab VitE cov tshuaj pab txo qhov kev pheej hmoo thiab tshwm sim ntawm AD; Txawm li cas los xij, lawv tsis tau tshaj tawm txog VitA, thiab pom tsis muaj kev sib koom ua ke ntawm VitB kom tsawg nrog AD [150] .Kev paub txog kev ua haujlwm hauv Asmeskas cov poj niam tau txhim kho zoo los ntawm kev kho mob ntev nrog retinoids [151]. Kev sim tshuaj kho mob ntawm RA thiab cov khoom siv sib txuas tuaj yeem paub meej tias nws cov txiaj ntsig kho tau zoo thiab lub luag haujlwm ua biomarker hauv cov neeg mob AD.Gut microbiota kuj tseem tuaj yeem cuam tshuam rau retinoid signaling hauv AD.

Dynamic plab microbiotamay ncaj qha txuas nrog retinoic acid los kho cov lus teb kho mob hauv AD [152]. Nyob rau theem AD thaum ntxov, tsis muaj kev sib raug zoo ntawm Retinol binding protein 4 thiab AD. Yog li ntawd, RBP4 tsis yog siv los ua biomarker nyob rau hauv thaum ntxov AD [153]. Kev ua tsis tiav ntawm RA signaling thiab koom nrog RA tsis txaus yog txuas nrog hnub nyoog txog kev paub txog kev poob qis hauv AD. Yog li, RAtherapeutic kev ua haujlwm yog txuas ncaj qha nrog AD thiab cov tsos mob cuam tshuam [154].Ob peb hom B vitamins (VitB9, VitB12, VitB6, thiab VitB2) koom nrog hauv kev kho cov metabolism ntawm homocysteine ​​[155].

Kev nce qib ntawm tag nrho cov ntshav plasma homocysteine ​​​​ua rau kev paub tsis meej, uas tuaj yeem ua rau dementia thaum kawg [66,156,157]. Ntau qhov kev tshawb fawb tau pom tias VitB supplementation txo qis tag nrho homocysteine ​​​​hauv kev kho mob rau kev txawj ntse poob [158–160]. Hauv kev txheeb xyuas tsis ncaj ncees, Douaud et al. qhia tias AD pathology, tus cwj pwm los ntawm atrophy ntawm cerebral grey teeb meem, raug txo los ntawm VitBsupplementation, txo tag nrho homocysteine ​​​​hauv ntshav ntshav [156]. Nyob rau hauv sib piv, ameta-kev tshuaj ntsuam ntawm randomized tswj kev sim qhia tau hais tias tsis muaj kev txhim kho nyob rau hauv kev txawj ntse tsis tau pom nyob rau hauv cov kev kho mob uas txo tag nrho homocysteine ​​​​nrog VitBsupplementation [161–163].

Xws li, tau los ntawm 26-lub lim tiam randomized, ob-dig muag, placebo- tswj kev kawm ntawm Taiwanese AD cov neeg mob tau muab cov tshuaj multivitamin ntxiv uas muaj cov vitamins B6, B12, thiab B9 ntxiv rau acetylcholinesterase inhibitor kev kho mob pom tau tias txo qis hauv cov concentration ntawm serum homocysteine ​​tab sis tsis muaj txiaj ntsig zoo ntawm kev paub lossis kev ua neej nyob txhua hnub ntawm cov neeg mob AD [164]. Lwm qhov kev tshawb fawb soj ntsuam tau pom tias qhov koob tshuaj ntau ntawm cov vitamins B (VitB9, VitB12, VitB6), thaum txo qis homocysteine ​​​​hauv qib, tsis cuam tshuam rau kev paub hauv cov tib neeg uas mob me me mus rau nruab nrab [165].

Txawm li cas los xij, hauv cov neeg mob MCI laus, cov vitamin B tiv thaiv kev paub txog kev poob qis uas tshwm sim los ntawm kev sim tshuaj placebo-tswj randomized [166]. Ntawm qhov tod tes, tsis muaj kev cuam tshuam ntawm 2- xyoo kev kho mob ntawm vitamin B ntawm qib siab ntawm homocysteine ​​​​thiab kev paub txog kev ua tau zoo raws li qhia los ntawm cov ntaub ntawv thib ob los ntawm RCT [167]. Cov vitaminB12 siab dua thiab folate tau nthuav tawm cov kev ua haujlwm kho mob muaj zog thiab txhim kho kev txawj ntse hauv kev kawm hla ntu ntawm AD [168].

Kev tshuaj xyuas ntawm presymptomatic AD tsis tuaj yeem kuaj pom los ntawm kev ntsuas cov ntshav folic thiab vitamin B12 qib raws li qhia los ntawm Turkish threecenter txoj kev tshawb fawb [169]. Yog li, lub luag haujlwm ntawm vitamin B thiab folic acid rau MCI thiab AD yog qhov xav tau thiab xav tau kev tshawb xyuas tiav. Yog li ntawd, kev soj ntsuam tag nrho ntawm kev kho mob zoo ntawm vitamin B thiab folate hauv MCI thiab AD ntawm cov pej xeem dav tuaj yeem daws qhov teeb meem uas tau hais los saum toj no.

Kev paub tsis meej tseem ceeb nrog kev nce qib ntawm thiamine deficiency. Cov tsos mob no tau txhim kho los ntawm kev ntxiv thiamine hauv cov tib neeg cuam tshuam [170]. Hauv cov neeg mob laus, kev hloov pauv hloov pauv tau cuam tshuam nrog qhov tsis muaj peev xwm ntawm cobalamin [171].

Vitamin B12 inhibits tau fibrillization thiab tsim ntawm cov neurofibrillary tangle.Yog li, VitB12 tiv thaiv tau aggregation thiab thaum kawg neurofibrillary tangle formation uas yuav ua rau qhov hnyav ntawm AD (Daim duab 3) [172]. Ib qho kev tshawb fawb hauv Havana, Cuba kuj qhia txog kev sib raug zoo ntawm qib ntawm homocysteine ​​​​thiab cov vitamins ntawm cov neeg laus AD. Nyob rau hauv txoj kev tshawb no, tag nrho ntawm 424 cov neeg saum toj no lossis sib npaug rau hnub nyoog 65 xyoo tau suav nrog uas 131 yog MCI, 43 AD, thiab, hauv 250 tus neeg, tsis pom qhov cim ntawm kev paub tsis meej.

Raws li piv rau cov neeg koom nrog noj qab haus huv, qib ntawm cov vitamin A, C, thiab B2 tau txo qis hauv cov neeg mob AD. Tsis tas li ntawd, hauv tib cov neeg mob AD thiab MCI cov neeg mob, qib homocysteine ​​​​tau nce siab piv rau cov tib neeg noj qab haus huv. Qib ntawm vitamin B12, folic acid, thiab thiamine tsis cuam tshuam rau txhua pawg. Cov kws sau ntawv xaus lus tias hauv MCI thiab AD, ntau yam vitamin deficiencies ncaj qha cuam tshuam rau kev puas tsuaj hauv cov metabolism ntawm homocysteine ​​[173].

Txawm hais tias qhov no yog ib qho kev kawm me me, yuav tsum muaj kev tshawb fawb loj ntawm cov pej xeem los nrhiav kev sib raug zoo ntawm cov vitamins B sib txawv thiab hyperhomocysteineemia ntawm AD thiab MCIpatients. Hauv cov neeg mob uas tsis muaj folate, qhov kev paub tsis meej tau raug kho los ntawm folatesupplementation rau lub sijhawm luv luv [174]. Kev mob plab yog ib qho tseem ceeb uas ua rau muaj kev loj hlob neurodegeneration hauv AD.

Ib qho kev sim tshuaj ntsuam pom tau hais tias folic acid qhia txog kev ua haujlwm ntawm cov khoom siv tshuaj tiv thaiv kab mob thiab tiv thaiv neurodegeneration hauv AD. ChiCTR-TRC13003246 yog tus lej sau npe ntawm qhov kev sim tshuaj no ua hauv Suav teb [175]. Kev nkag siab ntau dua ntawm qhov cuam tshuam ntawm VitB thiab homocysteine ​​metabolism rau kev paub txog kev ua haujlwm xav tau.Qhov kev pheej hmoo ntawm AD kuj nce ntxiv vim yog qib qis ntawm VitD [176,177].

Calcium ntau ntau thiab cov tshuaj parathyroid, nrog rau cov cytokines tshwj xeeb, tswj cov concentration ntawm daim ntawv nquag ntawm VitD, calcitriol. Daim ntawv tsis muaj zog ntawm VitD hla BBB, thiab, hauv glialand neuronal hlwb, nws hloov mus rau hauv daim ntawv nquag los ntawm enzyme CYP27B1 [178,179].Microglial hlwb kuj muaj lub luag haujlwm rau hloov provitamin D rau hauv daim ntawv nquag ntawmVitD [180]. Calcitriol tswj cov synthesis ntawm cov paj hlwb kev loj hlob (NGF) thiab thaum kawg tswj cov txheej txheem ntawm neuronal cell sib txawv thiab maturation. Tsis tas li ntawd, calcitriolregulates cov synthesis ntawm glial cell-line-derived neurotrophic factor (GDNF) [181,182] .Ob lub NGF thiab GDNF tswj kev kawm thiab kev nco los ntawm septohippocampalpathway. Nrog rau lub hnub nyoog nce qib, qib ntawm NGF txo qis [183].

Cov qib NGF kuj tseem txo qis hauv cov neeg mob AD [184]. Amyloid precursor protein (APP) concentration yog qhov ua tau zoo los ntawm NGF [184]. NGF teeb liab cuam tshuam ua rau muaj kev tswj hwm ntawm APPlevels thiab nce ntau lawm ntawm Abeta intracellular aggregates [185]. Qhov kev txaus siab ntawm kev paub txog kev ua haujlwm tau cuam tshuam los ntawm qib B12 raws li tau hais los ntawm cov neeg laus Korean-raws li kev tshawb fawb [187].VitE ua lub luag haujlwm tseem ceeb hauv kev txhim kho kev txawj ntse nrog rau kev nco tsis zoo [188]. VitE tuaj yeem ua ke nrog lwm cov tshuaj antioxidants los txhawb kev ua haujlwm ntawm cov tswv yim kho mob zoo [189]. Txawm hais tias muaj ntau yam pov thawj hais txog cov tshuaj tiv thaiv antioxidant ntawm VitE, lub luag haujlwm ntawm VitE yog qhov tsis sib haum xeeb [190].

Hauv qhov sib piv, kev sim tshuaj ntsuam xyuas txog kev ua haujlwm ntawm VitE hauv AD tau pom qhov tsis sib haum xeeb [190]. Ib qho kev sim no, qhia txog qhov cuam tshuam ntawm VitE ua ke nrog kev ua tiav ntawm kev paub tsis meej (MCI) cov neeg mob (thaum ntxov ntawm AD), pom tsis muaj txiaj ntsig ntxiv rau VitE supplementation [191]. Qhov kev tshawb nrhiav ob qhov muag tsis pom no tau kho cov neeg mob MCI nrog 2000 IU ntawm VitE txhua hnub thiab 10 mg ntawm cov tshuaj ua tiav txhua hnub lossis cov placebo rau peb lub xyoos.Tsis muaj kev cuam tshuam ntawm VitE rau MCI; Txawm li cas los xij, donepezil txo qis qhov kev nce qib ntawm MCI rau AD rau thawj 12 lub hlis thiab ntev dua rau cov neeg nqa khoom apolipoprotein E4 [192].

Kev ua haujlwm qeeb qeeb tau pom raws li qhov tshwm sim ntawm 2000 IU / d ntawm alpha-tocopherol hauv AD cov neeg mob piv rau kev tswj hauv kev sib koom ua ke randomized sim-raws li kev tshawb fawb [193].Nyob rau hauv xaus, vim nws tsis paub meej tias kev kho mob ntev thiab kev sib koom ua ke nrog VitE yog qhov zoo rau kev tswj hwm ntawm AD, kev tshawb fawb pej xeem dav dav yog xav tau [189].

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