Mechanisms Of Neuroplasticity And Brain Degeneration: Strategies for Protection Thaum Cov Txheej Txheem Kev Laus Part 3

Autophagic tsis ua haujlwm

Autophagy feem ntau txhais tau tias yog catabolic txheej txheem ntawm degradation thiab recycling, lub luag hauj lwm rau tshem tawm thiab zom cov cellular malformed los yog puas cellular cov ntsiab lus, organelles, thiab proteins (Wang li al., 2019).

Tsis muaj kev sib txuas ncaj qha ntawm lub plab zom mov thiab kev nco, tab sis peb cov khoom noj thiab kev noj qab haus huv ntawm lub cev tuaj yeem cuam tshuam rau peb lub hlwb kev noj qab haus huv thiab kev nco.

Yog tias peb lub cev muaj kev noj qab haus huv tsis zoo, xws li mob plab lossis kab mob plab xws li gastritis, nws yuav ua rau peb lub cev nqus tau cov as-ham, suav nrog cov vitamins thiab minerals uas muaj txiaj ntsig zoo rau lub hlwb. Qhov no tuaj yeem cuam tshuam rau peb lub hlwb noj qab haus huv, ua rau tsis nco qab lossis lwm yam teeb meem kev txawj ntse.

Yog li ntawd, nws yog ib qho tseem ceeb heev los tiv thaiv peb lub cev kev noj qab haus huv thiab kev noj qab haus huv ntawm lub plab zom mov, noj zaub mov kom zoo, thiab ua tib zoo saib xyuas lub cev. Tiv thaiv lossis tswj cov teeb meem kev noj qab haus huv ntawm lub cev los ntawm kev noj zaub mov zoo, kev tawm dag zog txhua hnub, thiab kev kuaj lub cev tsis tu ncua tuaj yeem pab peb lub hlwb noj qab haus huv thiab txhim kho peb lub cim xeeb.

Feem ntau, muaj qee qhov kev sib txuas ntawm lub cev kev noj qab haus huv thiab kev nco, yog li peb yuav tsum tau ua tib zoo saib xyuas lub cev kev noj qab haus huv thiab kev noj zaub mov kom zoo, kom peb lub cev tau txais kev noj qab haus huv txaus thiab kev noj qab haus huv, yog li txhawb lub hlwb kev noj qab haus huv thiab txhim kho peb lub cim xeeb. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche tuaj yeem txhim kho kev nco zoo vim Cistanche tuaj yeem tswj hwm qhov sib npaug ntawm cov paj hlwb, xws li nce qib ntawm acetylcholine thiab kev loj hlob, uas tseem ceeb heev rau kev nco thiab kev kawm. Tsis tas li ntawd, Cistanche deserticola tuaj yeem txhim kho cov ntshav khiav thiab txhawb nqa cov pa oxygen, uas tuaj yeem ua kom lub hlwb tau txais cov khoom noj txaus thiab lub zog, yog li txhim kho lub hlwb tseem ceeb thiab kev ua siab ntev.

Nyem paub cov tshuaj ntxiv los txhawb kev nco

Qhov no mechanism yog nyob ntawm lysosomal machinery thiab muaj ib tug high theem ntawm kev txuag ntawm eukaryotes, uas yog yooj yim piav vim hais tias nws muaj nuj nqi yog ib qho tseem ceeb los tiv thaiv thiab hloov cov kab mob nyob rau hauv ib tug stressful teeb meem kom txog rau thaum lub cell rov qab mus rau nws homeostasis xeev.

Tsis tas li ntawd, basal autophagyis tsim nyog heev raws li txoj kev ntxuav hauv cov khoom noj khoom haus ib txwm muaj, thiab tsis yog nyob rau hauv cov xwm txheej pathological. Qhov tseem ceeb tshaj plaws, los tiv thaiv cov hlwb los ntawm cov tshuaj lom ntawm cov proteins uas tsis tuaj yeem raug tshem tawm ntawm kev faib cell (Wang li al., 2019).

Autophagy tseem yog txoj hauv kev siv ntau tshaj plaws rau kev degradation ntawm cov kab mob hauv lub cev puas thiab cov protein sib xyaw ua ke (Wang li al., 2019).

Txij li thaum muaj cov protein aggregates yog ib qho muaj txiaj ntsig thiab muaj nyob rau hauv cov kab mob neurodegenerative feem ntau, suav nrog Alzheimer's (beta-amyloid thiab Tau plaques), Parkinson's (alpha-synuclein), thiab Huntington's (huntingtin) (Frake li al., 2015), autophagyis xav tau. los ua lub luag haujlwm tseem ceeb hauv kev tshem tawm cov toxicaggregates, los ntawm kev txo qis kev phom sij thiab tiv thaiv lub cell (Wang li al., 2019).

Tsis tas li ntawd, autophagy tuaj yeem tiv thaiv kab mob sib kis thiab txhawb kev tiv thaiv kab mob, ua lub ntsiab lus ntawm kev tiv thaiv kab mob tiv thaiv exogenous invaders (Rubinsztein etal., 2015). Ob leeg nyob rau hauv cov kab mob sib kis thiab nyob rau hauv cov mob uas pom nyob rau hauv neurodegenerative ntshawv siab, nws tau pom tias stimulation ntawm autophagy muaj kev tiv thaiv los ntawm preclinicaltrials (Rubinsztein li al., 2015).

Muaj cov kev tshawb fawb nrog ntau tus tsiaj ua qauv qhia tias thaum modulatingautophagy ntawm txoj kev mTOR-dependent (mammaliantarget ntawm rapamycin) muaj kev nce ntxiv hauv kev tshem tawm cov protein ntau (Menzies li al., 2017).

Tsis tas li ntawd, qhov inhibitionof autophagy tuaj yeem ua rau muaj kev phom sij ntawm cov protein no thiab ua rau muaj kev nce ntxiv hauv cov khoom sib xyaw (Frake li al., 2015). Qhov kev hloov pauv no tau ua tiav hauv kev tshawb fawb nrog cov tshuaj rapamycin thiab sawv cev rau kev cog lus zoo hauv cov kab mob nrog cov protein ntau (Frake li al., 2015; Menzies li al., 2017).

Muaj peb txoj kev sib txawv uas autophagy tuaj yeem ua cov qauv ntawm tes: macroautophagy, microautophagy, thiab chaperone-mediated autophagy (Frake li al., 2015).

Macroautophagy yog ib txoj hauv kev khaws cia hauv cov tsiaj txhu thiab lawv cov txheej txheem rov ua dua tshiab hauv cov xwm txheej autophagic. Nws muaj kev thauj mus los ntawm cov substrates mus rau lysosomes los ntawm kev tsim cov hlwv tsim los ntawm ib qho kev sib cais membrane, forminga ob chav membrane qauv hu ua autophagosome, uas ua raws li "insulating" qauv ntawm cov proteins thiab organelles.

Rau qhov degradation ntawm cov substrates yuav tshwm sim, lub autophagosome undergoes ib tug fusion nrog lysosome, yog li tsim ib autolysosome, nyob rau hauv uas tom qab no cov ntaub ntawv no yuav tawg thiab yuav recycled los ntawm lysosomal hydrolases (Menzieset al., 2017).

Autophagosome tsim yog tswj hwm los ntawm kev txiav txim los ntawm tsev neeg ntawm cov proteins hu ua ATG (AuTophaGy-txog) (Menzies li al., 2017), nrog rau Beclin1 / Vps34 complex yog qhov tseem ceeb nucleus rau kev tsim cov autophagosome, thiab tej zaum ob qho tib si txhawb thiab inhibit qhov pib ntawm cov txheej txheem autophagic, koom nrog cov kauj ruam tsis sib xws, suav nrog autophagosome biosynthesis thiab maturation (Pickford li al., 2008).

Hauv microautophagy, tsis zoo li macroautophagy, tsis muaj qhov tsim ntawm cov qauv nruab nrab ntawm autophagosome, uas muaj cov txheej txheem ntawm invagination lossis ncaj qha protrusion ntawm lysosomal membrane (Cuervo andWong, 2014), uas yog cov substrates degraded los ntawm lysosomalenzymes, uas tuaj yeem xaiv tau thiab tsis. - xaiv.

Cov txheej txheem no thiab nws cov txheej txheem hauv pathologies tseem tsis tau nkag siab, ib feem vim qhov nyuaj ntawm kev tsom xam.Chaperone-mediated autophagy, ntawm qhov tod tes, muaj txoj hauv kev tshwj xeeb (Cuervo thiab Wong, 2014).

Cov substrates yuav tsum tau degraded los ntawm txoj kev no yog cim los ntawm themotif uas muaj cov pentapeptide KFERQ (Lys-Phe-GluArg-Gln), uas tau lees paub los ntawm ib tug complex tsim nrog thecytosolic tshav kub shock protein (HSPA8 / HSC70), uas thauj cov substrate mus rau lub lysosome membrane. qhov twg nws unfoldsand khi rau monomers ntawm LAMP2A receptor (proteinassociated nrog lysosome membrane) (Cuervo thiab Wong, 2014).

Beclin1 (tseem hu ua Atg6) yog ib qho autophagic protein uas yog ib feem ntawm PI3K kinase complex thiab ua lub luag haujlwm tseem ceeb hauv kev tsim cov autophagosomes.

Kev txo qis hauv cov protein no tau pom nyob rau hauv lub hlwb ntawm cov neeg mob Alzheimer'sdisease (Furuya li al., 2005). Pickford thiab al. (2008) tau qhia txog lub luag haujlwm tseem ceeb ntawm Beclin1 hauv autophagy txij li lub khob ntawm Beclin1 noob hauv PDAPP nas ua rau muaj kev cuam tshuam rau cov txheej txheem.

Muaj kev nce ntxiv hauv cov khoom ntawm intraneuronal beta-amyloid, txo qis neuronal autophagy, neurodegeneration, lysosomal rupture, thiab microglialalterations, qhia txog kev raug mob neuronal. Nws kuj tau pom nyob rau hauv tib txoj kev tshawb fawb uas Beclin1 overexpression txo qis theem ntawm ob leeg intracellular thiab extracellular amyloid- .

Raws li Menzies et al. (2017), txawm hais tias muaj cov pov thawj loj hlob ntawm lub cev tseem ceeb ntawm autophagyin ib txwm muaj lub cev muaj zog neuronal, qhov chaw kho mob pathological tshwm sim ntawm cov kab mob neurodegenerative feem ntau raug cais tawm, yog li nws muaj peev xwm hloov me me hauv autophagicmachinery thiab ua rau rov ua dua tom qab ntawm cov aggregateshave cumulative cuam tshuam rau lawv tus kheej. hauv lub neej.

Tsis tas li ntawd, autophagy muaj cov txheej txheem tsis tshua muaj zog thiab tswj tau zoo heev, ua rau kev txheeb xyuas qhov tshwm sim nyuaj hauv thawj kauj ruam uas tsis muaj kev cuam tshuam txog kev lom neeg.

Noj tag nrho cov kev tshawb fawb no rau hauv tus account, cov txheej txheem tam sim no pom tau hais tias qhov txo qis hauv cov xwm txheej autophagic lossis lawv qhov kev puas tsuaj tuaj yeem ua rau Alzheimer's pathology.

Nws yog ib qho tseem ceeb uas tag nrho txoj kev autophagic, los ntawm cov theem induction mus rau theem tom ntej ntawm kev loj hlob thiab kev ua kom huv, yog tswj tau zoo heev. Nws tau pom tias cov kab mob tshwm sim los ntawm beta-amyloid tsub zuj zuj tshwm sim ib nrab los ntawm impairedautophagy, txoj hauv kev tseem ceeb rau kev degradation ntawm cytotoxic protein aggregates (Menzies li al., 2017).

Raws li cov ntaub ntawv pom nyob rau hauv cov kev tshawb fawb no, ib qho kev sim tau ua kom nkag siab txog kev sib raug zoo ntawm cov txheej txheem autophagy thiab cov txheej txheem uas qhov tshwm sim no tshwm sim nyob rau hauv cov ntsiab lus ntawm neuroprotection tiv thaiv cov kab mob neurodegenerative. Autophagy tej zaum yuav yog lub hom phiaj kho mob rau cov kab mob no.

Cell senescence, neurodegeneration thiab neuroprotection

Cell senescence yog ib qho tseem ceeb, multi-faceted agingmechanism txhais los ntawm irreversible cell voj voog raug txiav txim los ntawm ob peb mechanisms, xws li telomere shortening, ua kom oncogenes, oxidative kev nyuaj siab, thiab cell-rau-cellfusion (Biran li al., 2017; Cov me nyuam li al. , 2017).

Hauv qhov xwm txheej no, cells tsim SASPs uas suav nrog cov tshuaj tiv thaiv zoo licytokines thiab chemokines, kev loj hlob yam, thiab proteases.Qhov kev tso tawm ntawm cov xwm txheej no ua rau muaj kev tsim cov nuclei tsis tu ncua thiab pleomorphic mitochondria, txo qis inendoplasmic reticulum, thiab cuam tshuam ntawm Golgi apparatusleading mus rau qhov tsis zoo. ntau hom cell (Wang li al., 2019).

Kev zais ntawm SASPs ua rau muaj txiaj ntsig zoo hauv cov neeg nyob sib ze hloov cov ntaub so ntswg hauv zos. Qhov tseem ceeb tshaj tawm cov txiaj ntsig zoo ntawm SASPs (chemokines thiab cytokines) uas tau zais los ntawm cov hlwb senescent yog lub peev xwm los nrhiav cov neeg tua neeg kom tshem tawm cov qog hlwb.

Nyob rau tib lub sijhawm, cov teebmeem tseem ceeb txhawb nqa los ntawm SASPs yog qhov cuam tshuam ntawm cov qauv thiab kev ua haujlwm ntawm cov ntaub so ntswg ib txwm muaj, kev cuam tshuam ntawm kev hloov pauv ntawm cov hlwb epithelial thiab cov hlwb premalignant, thiab stimulation ntawm pre-malignant tab sis nonaggressive cancer hlwb kom txav mus thiab mus rau hauv. thebasal membrane (Chinta li al., 2015).Qee stressors yog classically txuas rau cell senescence.

Txawm hais tias tsis to taub tag nrho, cov kev ntxhov siab no ua rau tag nrho cov txheej txheem tau piav qhia saum toj no thiab tsim kom muaj qhov chaw zoo rau cov kab mob qog noj ntshav thiab neurodegeneration. Piv txwv li, phosphorylation ntawm tau protein tau txuas nrog kev tso tawm ntawm SASPs thiab kev txhawb nqa cov tshuaj toxicity hauv nruab nrab paj hlwb hlwb (Mendelsohn thiab Larrick, 2018).

Amyloid-plaques, aneuropathological marker ntawm Alzheimer's tus kab mob, kuj muaj feem xyuam rau cell senescence nyob rau hauv lub hlwb, ua rau lub hlwb progenitor oligodendrocyte tso tawm SASPs thiab tsim ib tug puas tsuaj ib puag ncig (Zhang li al., 2019). Hauv kev pom zoo nrog qhov no, qee cov neeg ua haujlwm ib puag ncig xws li tshuaj tua kab (paraquat) tuaj yeem ua rau cov cell senescence thiab ua rau - synucleinphosphorylation, nce qhov tshwm sim ntawm Parkinson'sdisease (Chinta li al., 2018).

Nrog rau tag nrho cov ntaub ntawv no, nws yog ib qho tseem ceeb los xav txog kev txhim kho cov tshuaj senolytic thiab cov tswv yim los tiv thaiv lossis kho cov cell senescence thiab txo qis qhov tshwm sim ntawm cov kab mob uas cuam tshuam txog kev puas tsuaj rau cov kab mob neurodegenerative. Ntau cov kev tshawb fawb tseem ceeb yog, yog li ntawd, ua kom nkag siab zoo dua cov txheej txheem ntawm cellenescence thiab ua ntej kev kho mob senolytic. .

Hydrogenperoxide (H2O2) yog ib qho piv txwv ntawm kev ntxhov siab uas ua rau muaj kev tso tawm ntawm ROS thiab ua rau cov cell senescence los ntawm oxidative stressinduction. Nyob ntawm qhov kev ntxhov siab, cov hlwb tuaj yeem ua rau muaj kev puas tsuaj loj uas ua rau necrosis, lossis kev puas tsuaj uas ua rau pib ntawm apoptotic mechanismsor cell senescence thiab kev loj hlob ntawm cov kab mob (deMagalhaes thiab Passos, 2018).

Txawm tias muaj ob peb lub hlwb tuaj yeem ua rau cov cellular thiab lub cev ua haujlwm tsis zoo, kev puas tsuaj ntawm cov ntaub so ntswg rov ua dua tshiab, thiab kev txhim kho ntawm cov tshuaj tiv thaiv kab mob (de Magalhaes thiab Passos, 2018). Txawm li cas los xij, hauv qee hom (cov nas spiny thiab luav, piv txwv li), muaj. yog cov txheej txheem ntawm kev tiv thaiv ntawm tes uas txuas rau kev tsim dua tshiab uas tsis muaj nyob hauv lwm hom (xws li nas thiab nas).

Nyob rau hauv cov tsiaj no, muaj ib tug nce nyob rau hauv cov kev txwv tsis pub rau mitochondria nyob rau hauv teb rau H2O2 kev nyuaj siab uas ua rau kom regenerative muaj peev xwm (Saxena li al.,2019). Cov txheej txheem no tuaj yeem muaj qhov cuam tshuam rau kev kho mob thiab kov yeej cell senescence thiab rau cov txheej txheem zoo sib xws uas tuaj yeem tshawb xyuas kom nce neuroprotection.

Muaj cov pov thawj ntxiv rau cov khoom tiv thaiv uas raug suav tias yog cov neeg ua haujlwm muaj peev xwm senolytic. Cov no suav nrog cov tshuaj paub zoo quercetin, piperlongumine, thiab curcumin uas twb tau siv los ua antioxidantsand neuroprotective, thiab tam sim no tau raug coj los ua naturalanalytics uas tuaj yeem txuas ntxiv kev noj qab haus huv (Liang li al., 2019).

Ntau cov kev tshawb fawb tau hais txog hauv vitro cell senescence los ntawm kev ntxhov siab thiab cov teebmeem ntawm senolytics, tab sis cov pov thawj invivo tsuas yog los ntawm kev tshawb fawb tsiaj nrog kev sib raug zoo rau tib neeg, feem ntau yog vim qhov sib txawv ntawm nas thiab tib neeg biology (Kirkland thiab Tchkonia, 2017).

Qhov kev cuam tshuam ntev ntawm cov khoom no, yog li ntawd, tseem yuav tsum tau tshawb xyuas, vim tias tsis yog txhua lub hlwb tsis zoo thiab yuav tsum tau muab tshem tawm (piv txwv li qhov txhab kho, suav nrog kev ua kom cov senescentcells).

Cov tswv yim uas tshem tawm cov senescent cell inductors hauv txoj kev sib npaug yuav yog tus yuam sij rau kev laus noj qab haus huv thiab "super agers" tshwm sim (cov neeg muaj hnub nyoog tshaj 85 xyoos, tsis muaj kev paub txog kev ua haujlwm, mob qog noj ntshav, lossis kab mob plawv), dhau ntawm cov cuab yeej cuab tam dav dav uas txhawb nqa qhov kev xav piav qhia. ncua kev noj qab haus huv nyob rau hauv cov pejxeem no (Halaschek-Wiener li al., 2018).

Cov tswv yim los tswj kev tiv thaiv lossis kev ua haujlwm ntawm cov neurons thiab astrocytes

Ob peb lub tswv yim tshuaj thiab tsis yog tshuaj kho mob tam sim no tau tsim los ua kom cov neuroplasticity thiab txhawb kev tiv thaiv neuroprotection lossis txawm tias neurogenesis. Hauv tsib xyoos dhau los, peb pab neeg tshawb fawb tau pom tias txoj kev ua neej tshwj xeeb yog neuroprotective, thiab siv cov no tuaj yeem hloov pauv txoj kev laus.

Nws tau pom tias kev kho mob ntev nrog microdoselithium carbonate (Li2CO3) tuaj yeem txo qis neuronal poob hauv hippocampus thiab nce neuronal ntom nyob rau hauv pre-frontalcortex ntawm cov nas transgenic rau Alzheimer's kab mob, as wellas nce qhov ceev ntawm BDNF nyob rau tib cheeb tsam (Nunes etal. , 2015). Tsis tas li ntawd, nyob rau hauv cov ntaub so ntswg hippocampal ntawm cov laus-ntxhiab nas nrawm nrawm 8 (SAMP-8) ib qho kev txo qis hauv kev ua haujlwm nuclear-kappa B thiab tso tawm proinflammatory cytokines tau pom tom qab kev kho mob microdoseLi2CO3, nrog rau kev nce hauv qhov ntom ntawm cov tshuaj tiv thaiv. inflammatory cytokine IL-10.

Raws li cov ntaub ntawv pov thawj, ntau cov kev tshawb fawb soj ntsuam luv luv tau ua tiav, qhia txog cov txiaj ntsig zoo ntawm microdose lithium hauv cov neeg mob uas tsis paub txog kev puas hlwb (MCI) lossis kuaj pom muaj Alzheimer'sdisease (Rybakowski, 2018). Hauv kev tshawb fawb nrog 61 cov neeg laus laus nrog MCI, piv txwv li, kev kho mob nrog qis qis ntawm Li2CO3 rau 24 lub hlis sib law liag txhawb kev ua haujlwm zoo dua hauv kev nco thiab kev saib xyuas, thaum piv rau cov placebo-kho cov hnub nyoog sib xws (Forlenza li al.,2019).

Tsis tas li ntawd, kev txiav txim siab tias Alzheimer's disease tuaj yeem ua rau muaj kev mob tshwm sim rau cov tib neeg uas muaj tus mob Down syndrome, qhov kev kho mob tsis ntev los no tau taw qhia txog qhov muaj peev xwm tiag tiag ntawm cov txiaj ntsig ntawm microdose lithium los tiv thaiv kev dementia ntxov hauv cov neeg no (Priebe thiab Kanzawa, 2020). Tseem tsom mus rau qhov Kev tiv thaiv ntawm neuroinflammation thiab oxidative kev nyuaj siab, kev tshawb fawb nrog tib neeg thiab nas qhia tias polyphenols tuaj yeem siv los tiv thaiv kev mob thiab cellular apoptosis (Spagnuolo li al., 2016).

Ib qho piv txwv yog, pomegranate, ib lub txiv hmab txiv ntoo uas muaj ntau ntau ntawm polyphenols nyob rau hauv lub pulp thiab tev (Yang li al., 2016). Peb pab pawg tau pom tias cov nas xa mus rau tus qauv neurodegenerative nrog theinfusion ntawm amyloid-beta peptide (1-42) thiab tom qab ntawd kho nrog pomegranate tev extract nthuav tawm nce hauv BDNF qib hauv hippocampus thiab txo qis hauv cov quav hniav ntom ntom, uas ua rau kev txhim kho spatial nco (Morz. ib., 2016). Nws ntseeg tau tias cov nyhuv neuroprotective ntawm pomegranate muaj feem xyuam rau kev tsim cov metaboliteurolithin, raws li nws twb tau pom tias cov compound no tuaj yeem inhibit qhov tsim ntawm senile plaques thiab tiv thaiv neurotoxicity (Yuan li al., 2016).

Lwm qhov muaj zog polyphenol uas muaj kev tshaj tawm txog kev tiv thaiv neuroprotective yog resveratrol.Nyob rau hauv kev sim nrog 60 tus neeg (60-79 xyoo), kev kho mob nrog cov tshuaj no txhawb kev khaws cia ntawm kev nco thiab kev txhim kho hauv kev nco txog kev paub txog cov qauv (Huhn li al., 2018).Raws li tau hais los saum toj no, nce qib BDNF yog ib qho cim ntawm kev tiv thaiv neuroprotection, vim tias kev ua haujlwm ntawm tropomyosin receptorkinase B receptors ua rau kev ua haujlwm ntawm PI3K / Akt neuroprotective antiapoptotic txoj kev (Kowianski etal., 2018).

Kev tawm dag zog lub cev yog lub tswv yim paub zoo uas nce BDNF thiab lwm yam tshuaj hormones xws li irisin, ua rau muaj kev txhim kho tseem ceeb hauv kev paub txog kev ua haujlwm, ob qho tib si tsiaj thiab tib neeg (de Meireles li al., 2019; Chen thiab Gan, 2019). Kev ua haujlwm nruab nrab ntawm lub cev rau 11 lub lis piam, piv txwv li, txhim kho kev txawj ntse ntawm cov nas uas tsis tshua teb rau kev ua hauj lwm amemory (nyob rau hauv ib qho kev tiv thaiv kev ua haujlwm) (Albuquerqueet al., 2016).

Ntxiv rau kev txhim kho kev txawj ntse, kev ua kom lub cev muaj zog txhawb nqa neurogenesis, tiv thaiv kev tuag ntawm neuronal, thiab ua rau muaj kev sib txawv neuronal, tsis zoo li lub cev ua si uas tsis tsim cov teebmeem zoo sib xws (Soet al., 2017).

Lwm qhov txiaj ntsig ntawm kev ua kom lub cev muaj zog yog qhov tso tawm ntawm irisin, ib qho tshuaj hormone tso rau hauv cov hlab ntsha los ntawm kev ua haujlwm ntawm Fndc5 noob los ntawm PGC-1 gene transcriptionco-activator (Ruth, 2012).

Irisin kuj txhawb kev txhim kho synapticfunction thiab tiv thaiv kev paub txog kev poob qis intransgenic Alzheimer's kab mob zoo li nas (Lourenco li al., 2019). Cov txiaj ntsig zoo sib xws kuj tau pom nyob rau hauv cov tsiaj uas muaj mob stroke thiab nce kev ua haujlwm ntawm PI3K / Akt thiab ERK 1/2 kev taw qhia txoj hauv kev tom qab kev tswj hwm ntawm irisin (Li etal., 2017).

Ob qho kev ua si lub cev thiab kev txhawb nqa ib puag ncig tau pom tias yog kev txhim kho kev nco thiab kev kawm nrog rau kev nce hippocampal neurogenesis (Sakalem li al., 2017), ua rau kev tsim kho ntawm kev txawj ntse.

Ina txoj kev tshawb fawb tsis ntev los no tau tshaj tawm los ntawm peb pab pawg, peb tau pom tias ib puag ncig muaj txiaj ntsig txhawb kev nco khaws cia hauv cov nas hloov pauv ntawm tus kab mob Alzheimer (Balthazaret al., 2018). Tsis tas li ntawd, nws twb tau pom tias kev txhim kho ib puag ncig tuaj yeem txhawb kev txo qis ntawm cov pro-inflammatory cytokine IL-1 thiab nce hauv astrocytes (Goncalves li al., 2018).

Hauv tib neeg, zoo li kev tawm dag zog lub cev muaj txiaj ntsig thaum ua haujlwm ntev. Kev tawm dag zog rau 12 lossis 16 lub lis piam, piv txwv li, tsis tau hloov pauv qhov tsis tseem ceeb cuam tshuam txog kev txhim kho kev paub zoo li kev nce ntshav hauv hlwb lossis kev loj hlob (raws li BDNF) (van der Kleij li al., 2018; Marston li al., 2019).

Txawm li cas los xij, cov tib neeg uas muaj kev ua haujlwm ntau dua rau lub sijhawm ntev (1 xyoos) tau pom tias muaj ntau dua hippocampal ntim (Clemenson li al., 2015). Cov ntaub ntawv no qhia tau hais tias kev txhim kho hauv kev paub txog kev ua tau zoo thiab neurogenesis tuaj yeem cuam tshuam rau lub neej muaj zog ntxiv.

Cov kev tshawb fawb no qhia meej meej tias txoj kev ua neej, thiab tsis yog kev kho mob nkaus xwb, tseem ceeb hauv kev txhawb nqa neuroprotection thiab neurogenesis. Yog li ntawd, cov kev tshawb fawb uas txheeb xyuas ob qho tib si pharmacological thiab non-pharmacologicalstrategies yog qhov tseem ceeb heev hauv kev tsim cov txiaj ntsig zoo.

Xaus

Thaum lub sij hawm kev laus, neuroplasticity thiab nco tau raug rau ib puag ncig tej yam kev mob uas cuam tshuam rau tib neeg 'genetic profiles thiab tej zaum yuav ua rau txoj kev loj hlob ntawm kev txawj ntse cia li zoo tag nrho cov kev noj qab haus huv nyob rau hauv cov neeg laus.

Neurodegeneration tuaj yeem hloov kho los ntawm kev hloov pauv hauv cell senescence, uas tuaj yeem txo cov neeg mob neuronaland glial cell, ua rau tsis ua haujlwm ntawm lub hauv nruab nrab lub paj hlwb.

Txawm li cas los xij, kev noj qab haus huv txoj kev ua neej tuaj yeem pab tswj hwm cov txheej txheem neuroprotective uas ua haujlwm tawm tsam cov txheej txheem ntawm tes tuag koom nrog hauv cov kab mob neurodegenerative.

Cov kev tshawb fawb ntxiv yog xav tau, tshwj xeeb tshaj yog nyob rau hauv vivo cov kev tshawb fawb thiab kev tshawb fawb tsom rau tib neeg lub hlwb, kom paub meej lub luag haujlwm ntawm cellenescence hauv neuroprotection thaum laus, txhawm rau txhim kho cov tshuaj senolytic, ntxiv rau muab pov thawj kev tshawb fawb ntxiv txog lub luag haujlwm ntawm kev tawm dag zog lub cev, kev noj haus zoo dua thiab ib puag ncig enrichment hauv kev txhim kho lub neej zoo thiab nce kev noj qab haus huv.

Sau cov nyiaj pab: MT, AARP, GSA, HNM, JM, thiab TAV sau cov ntawv nyeem.HSB thiab TAV tau kho cov ntawv nyeem. Txhua tus kws sau ntawv pom zoo rau qhov kawg version.Kev tsis sib haum xeeb ntawm kev txaus siab: Cov kws sau ntawv tshaj tawm tsis muaj kev tsis sib haum xeeb.

Kev txhawb nqa nyiaj txiag: MT tau txais kev kawm los ntawm Sao Paulo ResearchFoundation (2017/21655-6). HSB yog Brazilian National Council forScientific thiab Technological Development kws tshawb fawb (425838/2016-1,307252/2017-5). Txoj haujlwm no tau txais nyiaj txiag los ntawm Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – FinanceCode 001 thiab FAPESP (2016/07115-6).

Daim ntawv tso cai daim ntawv tso cai: Daim Ntawv Pom Zoo Daim Ntawv Tso Cai Copyright tau kos npe los ntawm txhua tus sau ua ntej tshaj tawm.

Plagiarism check: Tshawb xyuas ob zaug los ntawm iThenticate.Peer tshuaj xyuas: Externally peer-reviewed.Open access statement: Qhov no yog ib tug qhib-access journal, thiab cov khoom raug faib nyob rau hauv cov nqe lus ntawm Creative Commons Attribution-NonCommercial-ShareAlike 4.0

Daim ntawv tso cai, uas tso cai rau lwm tus los remix, tweak, thiab tsim los ntawm kev ua haujlwm tsis yog lag luam, tsuav yog qhov tsim nyog tau txais credit thiab cov kev tsim tshiab tau tso cai raws li cov ntsiab lus zoo ib yam.

Qhib cov neeg txheeb xyuas: Gabriele Siciliano, University of Pisa, Ltalis.Ntxiv cov ntaub ntawv: Qhib cov ntaub ntawv txheeb xyuas cov phooj ywg 1.

Cov ntaub ntawv

1. Akhter R, Sanphui P, Das H, Saha P, Biswas SC (2015) Cov kev cai ntawm p53 up-regulatedmodulator ntawm apoptosis los ntawm JNK/c-Jun txoj hauv kev hauv beta-amyloid-induced neuron death.J Neurochem 134:{{ 8}} ib.

2. Albuquerque M, Baraldi-Tornisielo T, Rotulo C, Caetano A, Martins A, Buck H, Viel T (2016) Treadmill qoj ib ce txhim kho kev nco evocation thiab upregulated alpha7 nicotinicreceptors ntom nyob rau hauv qis kev txawj ntse nas. Neuropharmacology 2: 1-6.

3. Andel R, Finkel D, Pedersen NL (2016) Cov teebmeem ntawm preretirement complexity thiab postretirement leisure ua si rau kev txawj ntse laus. J Gerontol B Psychol Sci Soc Sci71:849-856.

4. Ansari A, Rahman MS, Saha SK, Saikot FK, Deep A, Kim KH (2017) Function of the SIRT3mitochondrial deacetylase in cellular physiology, cancer, and neurodegenerativedisease. Hnub nyoog Cell 16:4-16.

5. Ashrafi G, de Juan-Sanz J, Farrell RJ, Ryan TA (2020) Molecular tuning ntawm axonalmitochondrial Ca(2+) uniporter xyuas kom cov metabolic yooj ntawm neurotransmission.Neuron 105:678-687.

6. Bading H (2017) Therapeutic targeting of the pathological triad of extrasynaptic NMDAreceptor signaling in neurodegenerations. J Exp Med 214:569-578.

7. Balduino E, de Melo BAR, de Sousa Mota da Silva L, Martinelli JE, Cecato JF (2020) Lub "SuperAgers" tsim nyob rau hauv kev kho mob: kev ntsuam xyuas neuropsychological ntawm cov neeg tsis paub ntawv thiab kawm ntawv cov neeg laus. Int Psychogeriatr 32:191-198.

8. Balthazar J, Schowe NM, Cipolli GC, Buck HS, Viel TA (2018) Enriched ib puag ncig zoo txo ​​cov plaques hauv cov nas transgenic qauv ntawm Alzheimer's kab mob, txhim kho kev nco. Pem Hauv Ntej Aging Neurosci 10:288.

9. Bazargani N, Attwell D (2016) Astrocyte calcium signaling: peb yoj. Nat Neurosci19:182-189.

10. Beeri M, Sonnen J (2016) Brain BDNF qhia ua biomarker rau kev txawj ntse reserveainst Alzheimer's kab mob. Neurology 86: 702-703.

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