Kev nce qib ntawm Alzheimer's Disease Related Glucose Metabolism Regulating Hormones Thiab Kev Tshawb Fawb Txog Kev Tshawb Fawb hauv Nootropics Ntawm Tshuaj Kho Mob

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Jia-Qi Zhao, Xiao-Qing Li, Yi-Ming Zhang, Mei-tong Guo, Cheng Han, Yang Shen, Qi Zhang, Shi-Feng Chu, Nai-hong Chen, Wen-Bin He

1 Shanxi Key Laboratory ntawm Suav Tshuaj Encephalopathy, Shanxi University of suav tshuaj, Taiyuan, Suav teb;

2 Lub Tsev Kawm Ntawv ntawm Materia Medica, Suav Academy ntawm Kev Kho Mob Sciences, Beijing, Suav.

Qhov tseem ceeb

Kab lus no tshuaj xyuas cov kev tshawb fawb uas txuas cov piam thaj metabolism-regulating cov tshuaj hormones rauAlzheimer tus kab mobthiab qhia tias qhov zoo ntawm Alzheimer's cov neeg mob tau txhim kho los ntawm kev tswj cov piam thaj metabolism. Vim tias muaj cov kev tshawb fawb txog kev kis mob loj heev uas tau tsim kom muaj kev sib koom ua ke ntawm cov kab mob metabolic thiab neurodegenerative mob feem ntau, thiab nws kuj tau pom tias cov kev hloov pauv ntawm cov tshuaj insulin tsis kam thiab cov piam thaj metabolism hauv AD zoo ib yam li cov ntshav qab zib, nws tau cog lus rau. nrhiav txoj hauv kev tshiab los xav txog cov tswv yim tshawb fawb ntawm kev tshawb nrhiav cov neeg sib tw nootropics rooting hauv tshuaj ntsuab thiab nws cov mis.

Cistanche tshuaj ntsuab tuaj yeem tiv thaiv thiab khoAlzheimer tus kab mob

Abstract

Alzheimer tus kab mobyog ib qho ntawm cov kab mob neurodegenerative, nws cov txheej txheem pathological tseem tsis meej. Muaj pov thawj tias ntshav qab zib muaj feem xyuam nrogAlzheimer tus kab mob. Txawm li cas los xij, lub hauv paus ua rau mob ntshav qab zib mellitus yog cov metabolism hauv qabzib tsis zoo. Tej zaum yuav muaj kev sib raug zoo ntawm cov piam thaj metabolism-regulating cov tshuaj hormones thiab Alzheimer's kab mob. Ntawm no, peb tshuaj xyuas cov kev tshawb fawb uas txuas cov piam thaj metabolism-regulating cov tshuaj hormones rau Alzheimer's tus kab mob, thiab hais tias qhov zoo ntawm Alzheimer's cov neeg mob tau txhim kho los ntawm kev tswj cov piam thaj metabolism.

Ntsiab lus: Alzheimer's disease; Mob ntshav qab zib; Glucose metabolism; Glucose metabolism - tswj cov tshuaj hormones

Anti Alzheimer's Disease: Cistanche

Glucose metabolism regulation hormone thiab AD

Insulin

AD thiab hom 2 mob ntshav qab zib mellitus (T2DM) yog ob hom kab mob feem ntau ntawm cov neeg laus. T2DM ntseeg tau tias yog qhov ua rau ntawm nws qhov ntxov tshaj plaws los ntawm kev txo qis ntawm cov ntaub so ntswg ib puag ncig mus rau cov tshuaj insulin, ua rau cov piam thaj tsis txaus siab [6]. Tias cov txheej txheem zoo sib xws ntawm intracellular insulin tsis kam thiab tsis txaus yog tshwm sim nyob rau hauv lub hlwb hauv cheeb tsam hauv AD tau dhau los ua pov thawj, suav nrog hauv cov tsis muaj ntshav qab zib [7].

Insulin yog ib qho hnyav molecular ntawm 6KD protein, zais los ntawm cov islet hlwb uas txhawb nqa los ntawm cov tshuaj endogenous lossis exogenous. Insulin tau raug suav tias yog ib hom tshuaj hormones uas tsis tuaj yeem dhau los ntawm cov ntshav-hlwb lub hlwb thiab tsuas yog muaj nyob hauv cov ntshav peripheral. Txog rau thaum xaus ntawm xyoo 1970s, thawj cov ntaub ntawv pov thawj tau muab tso rau pem hauv ntej tias insulin muaj nyob rau hauv lub hlwb nas los ntawm RIA txoj kev, qhov kev tshawb pom no tau pom tias insulin tuaj yeem dhau ntawm cov ntshav-hlwb teeb meem tuaj txog ntawm qhov chaw, yog li ntawd tuaj yeem hloov kho. Los ntawm cov chaw nruab nrab ntawm cov txheej txheem metabolic, ntxiv rau, cov neuron tuaj yeem tsim cov tshuaj insulin. Insulin receptor (IR) yog dav faib nyob rau hauv lub hauv paus paj hlwb (CNS), tshwj xeeb tshaj yog nyob rau hauv lub hippocampus, cortex, thiab lwm yam cheeb tsam txuam nrog leaming thiab nco [8]. Txij li thaum tshawb pom cov tshuaj insulin thiab insulin receptors uas twb muaj lawm hauv CNS tau luam tawm, ntau cov kev tshawb fawb pom tau tias cov tshuaj insulin nyob rau hauv nruab nrab cheeb tsam ua rau cov kev taw qhia xws li PI3K / Akt. Tsis tas li ntawd, cov paj hlwb txhawb nqa cov piam thaj los ntawm kev sib kho ntawm insulin [9] thiab tswj cov synaptic plasticity [10] los ntawm txoj kev qhia cov insulin hauv CNS.

Txoj kev taw qhia cov tshuaj insulin feem ntau koom nrog: (1) Phosphoinositide3-kinase (PI3K) txoj kev cuam tshuam nrog kev loj hlob ntawm tes thiab kev loj hlob [11]; (2) mitogen-activated protein kinase (MAPK) txoj kev tswj hwm ntawm tes sib txawv [12]. PI3K / Akt plays lub luag haujlwm tseem ceeb hauv txoj kev taw qhia cov tshuaj insulin. Insulin resistance (IR) yog insensitive rau insulin hauv lub cev. Cov kev tshawb fawb pom tau tias muaj cov kab mob insulin txawv txav thiab cov tshuaj insulin tsis kam uas tshwm sim hauv cov neeg mob AD lub hlwb. Insulin tseem cuam tshuam AB ntau lawm thiab tshem tawm [13]. Lub ntsiab tseem ceeb ntawm A yog amyloid precursor protein (APP) hydrolysis. Lub hydrolysis ntawm APP tau tshwm sim los ntawm PI3K / Akt signaling txoj hauv kev thaum insulin tsis kam tshwm sim, uas ua rau nce A thiab kev cuam tshuam ntawm kev thauj mus los ntawm A. Thaum kawg, senile plaques tsim nyob rau hauv lub hlwb [14]. Txawm li cas los xij, glycogen synthase kinase (GSK) yog ib qho tseem ceeb ntawm PI3K downstream kinases. Thiab nws txoj haujlwm tuaj yeem ua rau tau qhov tsis txaus ntseeg phosphorylation thiab thaum kawg tshwm sim NFTs [15]. Amylin

Amylin yog pancreatic-cell hormone co-tso tawm nrog insulin hauv kev teb rau kev noj zaub mov. Nws txo qis orexis, gastric acid secretion, txwv tus nqi ntawm plab hnyuv, thiab txo qis pancreatic glucagon secretion [16]. Nws yog qhov tseem ceeb thib peb ntawm cov tshuaj hormones hauv lub txiav thiab tswj cov ntshav qab zib kom sib npaug nrog insulin. Hauv lub xeev pathological, qib siab ntawm cov ntshav amylin muaj kev cuam tshuam rau insulin secreted thaum hyperglycemia.

Muaj ntau qhov sib xws ntawm amylin thiab muaj pes tsawg leeg ntawm A. Piv txwv li, lawv muaj ib qho piv txwv theem nrab qauv [17], uas khi rau lub cev amyloid receptor [18]. Tau degraded los ntawm tib yam Insulin-degrading enzyme thiab cuam tshuam nrog ib leeg hauv txoj kev nyuaj [19].

Emerging qhia hais tias tseem ceeb hais tias amylin impairs cerebrovascular los ntawm amyloid deposition nyob rau hauv cov neeg mob AD [20]. Lub caij no, cov neeg mob AD muaj cov ntsiab lus siab ntawm amylin qhia hauv cov ntshav. Yog li ntawd, muaj kev sib raug zoo ntawm amylin thiab AD, uas tej zaum yuav yog qhov thib ob amyloid protein nyob rau hauv lub hlwb ntawm AD. Tsis tas li ntawd, qhov kev sim fluorescent labeling ua pov thawj tias cov amylin feem ntau yog muab faib rau hauv cov neurons paub tab nyob rau hauv lub hlwb ntawm nas, nrog rau feem ntau faib nyob rau hauv lub cortex, ua raws li hippocampus thiab lwm qhov chaw. Nrog rau kev nce ntawm lub hnub nyoog ntawm AD qauv nas, kev qhia ntawm amylin hauv thaj tsam cortical yog maj mam nce thiab tsim cov plaques, uas yog cov lus qhia nrog A [21l. Hauv qhov xwm txheej ntawm lub cev, amylin tuaj yeem poob rau cov ntshav qab zib, tab sis lub sijhawm ntev ntawm cov ntshav qabzib siab tuaj yeem ua rau muaj qib ntawm amylin ntau dua, uas tuaj yeem dhau los ntawm cov hlab ntsha-hlwb thiab tsim kev sib sau ua rau tsis zoo rau cov neurocyte, thaum kawg ua rau poob qis hauv cov hlab ntsha. muaj peev xwm ntawm leming thiab nco.

Glucagon zoo li peptides

Glucagon-zoo li peptides yog ob hom glucagon-zoo li peptide-1(GLP-1) thiab glucagon-zoo li peptide-2(GLP-2). Ib qho, GLP-2 yog ib qho kev loj hlob ntawm plab hnyuv. Lwm qhov, GLP-1 yog peptide secreted uas ua raws li qhov tseem ceeb ntawm cov ntshav qabzib homeostasis los ntawm kev tsim txiaj ntawm nws lub peev xwm los ua kom qeeb plab hnyuv, txhim kho pancreatic insulin secretion, thiab inhibit pancreatic glucagon secretion. GLP{10}} yog tso tawm los ntawm L hlwb ntawm lub plab hnyuv mucosa nyob rau hauv cov lus teb rau ib pluag mov, thiab cov ntshav-glucose-txo cov yeeb yam [22]. GLP-1 secretion yog ze ze rau cov khoom noj muaj pes tsawg leeg. Qhov tseem ceeb, GLP-1 tau nce ntxiv tom qab noj cov khoom noj muaj suab thaj thiab rog [23]. Nws muaj lub luag haujlwm tseem ceeb hauv lub cev hauv CNS.

GLP-1 receptors feem ntau yog faib rau hauv hypothalamus, deutocerebrum, thiab tritocerebrum. Ua kom lub GLP-1 receptor nyob rau hauv cov cheeb tsam ntawm lub paj hlwb tuaj yeem tswj kev qab los noj mov thiab txo cov khoom noj, uas tuaj yeem tswj kev qab los noj mov thiab txo cov zaub mov noj [24].

Adenylate cyclase tau qhib thaum GLP-1 khi rau GLP-1 receptor nyob rau saum npoo ntawm cell membrane, thiaj li tuaj yeem txhim kho Cyclic Adenosine monophosphate (cAMP) qib, qhib PKA, cAMP- tswj guanine nucleotide. Kev sib pauv yam II (Epac2), yog li txhawb nqa nyob rau hauv qabzib-stimulated insulin secretion. Qhov sib txawv ntawm cov piam thaj-dependent insulin secretion effect, GLP-1 txhawb nqa kev loj hlob thiab kev sib txawv ntawm cov hlwb tsis muaj qhov concentration ntawm cov piam thaj, uas tuaj yeem tsim hauv cov ntshav qabzib. GLP-1 receptor downstream ntau txoj kev taw qhia muaj kev koom tes hauv kev txhawb nqa kev loj hlob, kev sib txawv, thiab kev tiv thaiv cov hlwb.

GLP-1 tsis tsuas yog tswj cov ntshav qabzib hauv cov ntshav peripheral tab sis kuj ua haujlwm hauv cov neurotransmitter hauv CNS, uas ua lub luag haujlwm tseem ceeb hauv cell proliferation, apoptosis, thiab neurogenesis [25]. Lub caij no, ua ke nrog cov neeg txais kev sib raug zoo, GLP-1 koom nrog PI3K thiab MAPK teeb liab txoj hauv kev, uas tuaj yeem qhib cov dej hauv qab ntawm PKA, txhawb kev tso tawm neurotransmitter, thiab txhim kho synaptic plasticity[26]. Nyob rau tib lub sijhawm, nws tsis yog tsuas yog them nyiaj rau cov teeb liab insulin, txhim kho qhov tshwm sim ntawm insulin tsis kam ntawm cov neeg mob AD. Qhov kev sim pom tias GLP-1 analogs tau txhim kho cov txiaj ntsig ntawm lub cim xeeb uas tau txhaj A [27], thiab txo qhov tsim ntawm A [28].

Cov txiaj ntsig ntawm cistanche khoom:Anti Alzheimer tus kab mob

Asprosin

Asprosin raug txiav tawm ntawm qhov kawg ntawm myofibril protein-1, uas muaj 140 amino acids ntu. Nws tuaj yeem txhawb kev decomposition ntawm daim siab qabzib los ntawm G protein nyob rau hauv-cAMP-PKA txoj hauv kev, thiab pab txhawb kev nqus cov piam thaj mus rau hauv cov hlwb kom cov ntshav nyob rau qib siab [29]. Cov kev tshawb fawb yav dhau los tau pom tias cov neeg mob neonatal progeroid syndrome (NPS) muaj cov tshuaj insulin tsis kam [30]. Los ntawm kev tshuaj xyuas yav dhau los, peb tuaj yeem ntes tau tias AD muaj kev sib raug zoo nrog insulin tsis kam.

Cov kws tshawb fawb tau tshawb pom tias tus qauv nas ntshav qab zib tau nce qib siab dua li lub voj voog ib txwm ntawm Asprosin, tom qab ntawd nws tau txhaj tshuaj tiv thaiv kab mob monoclonal rau kev sib xyaw nrog Asprosin, uas tuaj yeem tswj cov qib insulin. Yog hais tias insisting rau kev kho mob, cov insulin tsis kam rov qab mus rau qhov qub [31]. Kev txhim kho insulin tsis kam ua lub luag haujlwm tseem ceeb hauv kev txo qis qhov tshwm sim ntawm AD.

Glucocorticoids

Glucocorticoids (GC) tau zais los ntawm adrenal cortex zonafasciculata. Hauv tib neeg, cortisol yog lub hauv paus tseem ceeb, thaum, hauv cov nas, nws yog corticosterone. Nws muaj kev ua haujlwm ntawm kev tswj cov metabolism ntawm glycolipid thiab cov protein, thiab tseem tiv thaiv kev tiv thaiv kab mob, tiv thaiv kev mob thiab tiv thaiv kev poob siab. Kev tso tawm yog tswj hwm glucocorticoid hypothalamic-pituitary-adrenocortical axis (HPA) [32]. Lub hauv paus tseem ceeb ntawm cov lus teb kev ntxhov siab yog ua kom HPA thiab txhawb lub adrenal cortex kom tso tawm glucocorticoids.

GC yog cov tshuaj steroid uas dhau los ntawm cov ntshav-hlwb thaiv kev sib txuas nrog cov receptors. Glucocorticoid muaj ob lub receptors nyob rau hauv lub hlwb, ib tug yog mineralocorticoid receptors (MR) nrog siab affinity, thiab lwm yam yog glucocorticoid receptor (GR) nrog tsawg affinity, Cov receptors no tau qhia feem ntau nyob rau hauv lub hippocampus cheeb tsam, qhov twg GR tau qhia nyob rau hauv lub cal cheeb tsam. [33]. GC qib siab ib ntus tuaj yeem txhim kho kev nco, qhov kev pheej hmoo siab ntawm GC ua rau GR nquag ua haujlwm tsis tu ncua, uas tuaj yeem ua rau lub cev nco ua haujlwm [34].

Cov kev tshawb fawb pom tau hais tias qib cortisol hauv cov ntshav, qaub ncaug, lossis cov kua cerebrospinal ntawm cov neeg mob AD yog siab dua li cov neeg ib txwm muaj. Cov kev hloov pauv hauv cov qib cortisol muaj qhov cuam tshuam zoo nrog lub cim xeeb cia ntawm AD, tab sis cov txheej txheem tsis meej [35]. Lub hippocampus yog qhov chaw siab tshaj ntawm HPA axis tswj. Thaum cov kab mob hippocampal hauv cov neeg mob AD, kev ua haujlwm ntawm HPA axis cuam tshuam, thaum GC qib siab. Qhov no ua rau cov dendrites ntawm hippocampal neurons mus rau atrophy, poob, rov tsim dua, thiab thaum kawg, kev txawj ntse poob tshwm sim. Nyob rau tib lub sijhawm, qib siab ntawm GC ua rau APP hydrolyze sai dua, thiab ua rau muaj kev sib txuam ntawm A loj dua. Hloov pauv, qhov tso nyiaj ntawm A yuav ua rau nce qib ntawm GC, tsim lub voj voog tsis zoo, thiab ua rau cov xwm txheej ntawm AD ua rau hnyav dua. Qhov siab ntawm GC hauv lub hlwb txhawb kev ua haujlwm ntawm GSK3 kinase thiab nce qhov txawv txav ntawm phosphorylation ntawm tau protein ntau [36].

tshuaj ntsuab: Cistanche

Kev Tshawb Fawb Txog Kev Tshawb Fawb hauv Nootropics ntawm Herbal Tshuaj

Raws li tau hais los saum toj no, qhov txawv txav ntawm cov piam thaj metabolism thiab nws cov tshuaj hormones muaj feem cuam tshuam nrog qhov tshwm sim thiab kev loj hlob ntawm AD. Txawm hais tias lub ntsiab theories ntawm AD pathogenesis tau npaj tseg, uas yog cholinergic hypothesis thiab beta-amyloid cascade hypothesis, cov txheej txheem tseem yuav tsum tau piav qhia. Clinically, cov tshuaj kho AD feem ntau suav nrog cov tshuaj tiv thaiv cholinesterase donepezil, lith's amine, galanthamine, thiab glutamate receptor antagonist memantine. Txawm li cas los xij, AD tseem tsis tuaj yeem tiv thaiv lossis kho tau zoo. Lub caij no, cov tshuaj no muaj ntau yam kev mob tshwm sim ntxiv rau qhov ntev ntawm kev kho. Cov pov thawj tshwm sim qhia tau hais tias kev cuam tshuam ntawm cov tshuaj ntsuab muaj cov yam ntxwv ntawm cov kev mob tshwm sim me me thiab kev nyab xeeb siab, uas ua rau nws muaj qee yam zoo hauv kev kho mob ntawm AD.

Ib pab pawg tshawb fawb tshuaj ntsuab pom nyob rau hauv lawv cov kev tshawb fawb yav dhau los uas curcumin txo qis kev sib sau ua ke hauv AD nas hlwb, thiab txhim kho cov tsos mob ntawm kev nco tsis zoo. Tsis tas li ntawd, lawv siv immunohistochemistry thiab western blot cov tswv yim los kuaj xyuas cov piam thaj metabolism thiab insulin txoj hauv kev hauv APP transgenic nas. Cov txiaj ntsig tau pom tias curcumin ameliorated qhov tsis muaj peev xwm ntawm insulin signaling txoj hauv kev thiab txhim kho spatial kev kawm thiab kev nco muaj peev xwm los ntawm kev tswj cov kev qhia ntawm insulin zoo li kev loj hlob protein [37]. Durairajan et al. qhia tias berberine inhibited amyloid precursor protein phosphorylation los tiv thaiv A deposition [38]. Ib txoj kev tshawb fawb tau pom tias DanHong Txhaj Tshuaj tuaj yeem txhim kho kev nco muaj peev xwm ntawm cov neeg mob ntshav qab zib [39]. Hauv kev sim tshuaj, noj DanShenDiWan tuaj yeem txo qhov kev tso tawm thiab txhim kho kev paub txog kev ua haujlwm hauv cov neeg mob ntshav qab zib [40]. ZhengSunetal tau pom tias daim ntawv qhia ZiBuPiIYin tuaj yeem tiv thaiv kev puas hlwb hauv cov nas mob ntshav qab zib. Cov txheej txheem tuaj yeem cuam tshuam nrog kev txhim kho kev ua haujlwm tsis zoo ntawm mitochondrial, insulin tsis kam, thiab txo qhov mob A [41]. Suav tshuaj yog raws li sau los ntawm complex kev sib cuam tshuam, nyob rau hauv lwm yam lus, xav tau kev tshawb fawb ntau ntxiv ntawm cov synergistic los ntawm cov tshuaj ntsuab ua ke kom nkag siab zoo dua cov txheej txheem rau cov kab mob [42].

Ib txoj kev tshawb fawb txog kev kis kab mob loj heev tau tsim kom muaj kev sib koom ua ke ntawm cov kab mob metabolic thiab neurodegenerative disorders feem ntau [43]. Nws kuj tau pom tias qhov kev hloov pauv pathologic ntawm insulin tsis kam thiab cov piam thaj metabolism hauv AD zoo ib yam li cov ntshav qab zib. Yog li ntawd, nws tau cog lus tias yuav nrhiav tau txoj hauv kev tshiab los xav txog kev tshawb fawb lub tswv yim ntawm kev tshawb nrhiav cov neeg sib tw nootropics hauv paus hauv tshuaj ntsuab thiab nws cov mis.

Neuroprotective teebmeem ntawm cistanche

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