Na Cocer Peptides bin rayt am 
1 mɔnt dɔn pas
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Ovaviu fɔ di tin dɛn we dɛn dɔn lan
dis atikul de εksplכr di mεkanism dεm we di senesεnt sεl dεm de kכntribyut fכ di biginin εn prכgreshכn fכ di Alzaima sik (AD). Alzaima sik na wan kɔmɔn nyurodijɛnɛraytiv disɔda we kin afɛkt di ol pipul dɛm mɔ, we kin sho se dɛn nɔ kin ebul fɔ ɔndastand dɛnsɛf ɔltɛm ɛn dɛn nɔ kin ebul fɔ biev fayn. As di pipul dɛm na di wɔl de ol, di wan dɛm we gɛt AD de kɔntinyu fɔ bɔku ɛvri ia, we de put bɔku lod pan di sosayti ɛn famili. pan ɔl we dɛn dɔn mek bɔku prɔgrɛs pan AD risach, di ɛksaktɔ etiɔlɔji ɛn di pathogenesis nɔ klia yet. as wan pan di praymar risk fכ AD, sεlyul senesεns dεn gεt inkrεsiv atεnshכn insay di rεsεnt ia fכ in rol fכ di patכjεnεsis fכ AD. di akyumyuleshכn fכ di senesεnt sεl dεm na di bכdi de kכlכsכl wit di biginin εn prכgreshכn fכ difrεn sik dεm we de kכmכt frכm di ej. di senesεnt sεl dεm de ple imכtant rol insay di patכlayz prכsεs fכ AD, εn fכ elucidate dεn mεkanism dεm fכ akshכn na big minin fכ divεlכp nyu tritmεnt fכ AD.
Figure 1. Alzaima sik pathogenic protin dεm de kכntribyut to di bren sεl dεm we de sεn. (a) Ovaviu fכ di intarakshכn bitwin senesεnt bren sεl dεm wit amyloid plek dεm εn pathogenic tau. (b–e) Ditayl vεyu fכ εvri rispεktiv sεl tכp εn senesεns-asכsiet fכm dεm we dεn ripot insay di litεrachכ: (b) nyuron, (c) maykroglia, (d) oligodεndrכsayt/oligodεndrכsayt prεkursכr sεl, (e) astrosayt, εn (f) blכd-bren barεri (BBB) we de sho εndoteyl sεl dεm, pεrisεt, εn astrosayt dεm, we de sho kompromis BBB integriti in AD.
Ovaviu fɔ di Sɛnesɛnt Sɛl dɛn
(1) Difinishכn εn kכntribyushכn dεm fכ di sεl dεm we de sεn
sεnesεns de tכk bכt di rεvεrsibl growth arest fכ di sεl dεm afta dεn dכn כnda wan sכm nכmba fכ divεlכpmεnt כ we dεn εkspos to difrεn strεs fכktכ dεm (lεk כksidεtiv strεs, DNA dεmεj, tεlomεr sכt, εtk). di senesεnt sεl dεm de sho yunik fεnotaypik kכntribyushכn dεm, inklud inkrεs sεl vכlyum, flat, εn εlevεt β-galactosidase (β-gal) aktiviti, we na bayolojikal mak we dεn kin yus fכ no di senesεnt sεl dεm. apat frכm dat, senesεnt sεl dεm de sho upregulashכn fכ sayklin-dipεndεnt kinase inhibito dεm (lεk p16INK4a εn p21Cip1), we de inhεbit sεl saykl prכgreshכn, we de mek sεl dεm arεst insay di G1 fεz כ G2/M fεz εn dat de mek dεn nכ de divεlכp mכr.
Mekanism dεm fכ Senesεnt Sεl Fכmeshכn
1. כksidεtiv strεs εn DNA dεmεj: כksidεtiv strεs na di kכl indyuz fכ sεlyul sεnesεns. כnda nכmal fysiolojikal kכndishכn dεm, di prodyushכn εn kliarεns fכ riaktiv כksijεn spεshal (ROS) insay sεl dεm de insay dinamik ikwilεbri. כltu, we dεn de ol כ כnda sכm patכlayz kכndishכn dεm, di inkrεs pan ROS prodakshכn de mek di DNA dεm dεm. we di DNA dεm we dεn dכn pwεl de kכmכt to sכm mak εn dεn nכ kin rεpεr am fayn fayn wan, wan siriכs signal path dεm de aktibכt, lεk di p53-p21 εn p16-Rb signal path dεm, we de mek di sεl dεm go insay wan senesεnt stet. insay di bren tisu frכm Alzaima sik pasεnshכn dεm, di כksidεtiv strεs lεvεl dεm de sכmtεm εlevεt, we de mek di DNA dεm we de dכn inkrεs na di nyuron dεm εn di glial sεl dεm, we in tכn de mek di sεl dεm sεnesεns.
2. di tεlomεr dεm we de sכt: di tεlomεr dεm na rεpεtitiv DNA sikεns dεm na di εnd dεm na di kromozom dεm we de sכt sכmtεm wit di sεl dεm we de sheb. we di tεlomεr dεm sכt to wan sכm lεngth, dεn kin mek di signal dεm we di tεlomεr dεm de sכt. insay nyural stεm sεl dεm, di tεlomεr sכt de kכlכsכl wit di biginin fכ senesεns, we kin impεr di sεlf-rinual εn difrεns kapasiti fכ nyural stεm sεl dεm, we de afekt di nכmal divεlכpmεnt εn fכnshכn fכ di nεv sistεm.
di mεkanism fכ akshכn fכ di senesεnt sεl dεm na di alzaima sik
(1) Indukshɔn fɔ Nyuroinflameshɔn
1. di Rol we di Senescence-Asosiated Secretory Phenotype (SASP) de ple: di senescent sεl dεm de sho wan yכnik sekret fεnotayp we dεn kכl di senescence-associated secretory phenotype (SASP). SASP kכmכp difrεn saytokכn dεm, kεmokin dεm, growth fכktכ dεm, εn proteas dεm, lεk intalyukin-6 (IL-6), intalyukin-8 (IL-8), εn tכmכro nεkrכsis fכktכ-α (TNF-α). insay di bren tisu fכ di pipul dεm we gεt Alzaima sik, di senesεnt glial sεl dεm εn nyuron dεm de sekret bכku SASP fכktכ dεm, we kin mek di imyun sεl dεm we de rawnd am aktibכt εn trigεr krεse inflammatory rεspכns. IL-6 εn TNF-α de promuot di aktibכshכn fכ maykroglia, we de mek dεn transishכn frכm wan kwεshכn stet to wan pro-inflammatory stet, we de rilis mכr inflammatory mεdiate dεm εn fכ mek nyuroinflameshכn mכr. dis krכnik inflammatory envayroment de damej nyuron dεm, impεr di sinaptik fכnshכn, εn de mek di kכgnitiv disfכnkshכn.
2. ifekt pan glial sεl dεm: di ol we di astrosayt dεm εn maykroglia de ol de ple wan kכl rol fכ AD nyuroinflameshכn. di astrosayt dεm we de ol de sekret SASP fכktכ dεm we de protεkt di agregεshכn εn diposishכn fכ β-amyloid (Aβ) we de inhεbit in kliarεns. di ol we di maykroglia de ol de ridyus dεn abiliti fכ fagosayt Aβ, we de mek di Aβ plek dεm nכ de kכmכt fayn fayn wan na di bren. Bifo dat, dεn de rilis mכr inflammatory factors, we de mek wan bad bad saykl we de mek nyuroinflammation εn nyurodijεnεreshכn bכku.
Figure 2 Mak dεm fכ sεlyul sεnesεns de inkrεs na di bren fכ hTau mays dεm we de mכdel tauopathy fכ AD.
(2) Prɔmoshɔn fɔ Nyurodijɛnɛreshɔn
1. dayrekt damej to nyuron dεm: sכm saytokכn dεm εn proteas dεm we di sεl dεm we de sכmtεm de kכmכt kin damej nyuron dεm dairekt wan. matris mεtaloproteinεz dεm (MMP) na wan pan di kכmכpכnεnt dεm fכ di senesεns-asכsiet sekretכm (SASP), we kin dεgrad di εkstrasεlula matris εn nyurotransmitta-rεlatεd protin dεm, we de disrupt di strכkchכ εn fכnshכn fכ nyuron dεm. di ROS we di senesεnt sεl dεm de prodyuz kin mek כksidεtiv damej bak to nyuron dεm, we kin mek nyuronal apoptosis εn day. insay di bren tisu fכ AD pasεnshכn dεm, nyuronal senesεns de kכlכsכl wit sεl dεm we de day, we kin bi wan pan di ki fכs tin dεm we de kכntribyut to kכgnitiv disfכnkshכn.
2. Intafεreshכn wit Nyurotransmit Transmishכn: di prεsεns fכ senesεnt sεl dεm kin disrupt di sεntesis, rilis, εn transmishכn fכ nyurotransmit dεm bak. inflammatory factors kin inhibit di sεntesis fכ acetylcholine, wan nyurotransmitta we implεnt fכ mεnten nכmal kכgnitiv fכnshכn. apat frכm dat, sכm tin dεm we di senesεnt sεl dεm de sekret kin afekt di εksprεshכn εn fכnshכn fכ di nyurotransmit rεsεpכta dεm, we kin mek di nyurotransmitta signal we nכ nכmal, i kin mek di kכmyunikeshn εn infכmeshכn prכsεsin bitwin nyuron dεm bכku mכr, εn dat kin mek di kכgnitiv impεryans.
(3) Chenj dɛn we de apin na di Kɔmyunikeshɔn we de bitwin di sɛl dɛn
1. Abnכmal Parakrin Sayn: di senesεnt sεl dεm de kכmכnik wit di sεl dεm we de rawnd tru parakrin signal bay we dεn de sekret SASP fכktכ dεm. dis fכs tin dεm kin afekt di fכnshכn εn fεt fכ di neba sεl dεm, we kin mek di intasεlula kכmכnikεshכn nεtwכk de disrupt. insay di bren tisu fכ AD pasεnshכn dεm, SASP fכktכ dεm we di senesεnt glial sεl dεm de sekret kin afekt nyuronal growth, sכvayv, εn difrεns, we i de infכlכw bak di maykro envayroment fכ nyural stεm sεl dεm, inhεbit dεn proliferashכn εn difrεns, we de afekt nyural rigεnεreshכn εn ripa prכsεs dεm.
2.Disrupshכn fכ intasεlula kכnεkshכn dεm: di senesεnt sεl dεm kin disrupt intasεlula kכnεkshכn strכkchכ dεm bak, lεk tayt jכnkshכn dεm εn gap jכnkshכn dεm. insay di bכdi-bren barεri, senesεns fכ di εndoteyl sεl dεm de lid to ridyus εksprεshכn fכ tayt jכnkshכn protin dεm, we de inkrεs di pεrmiabiliti fכ di bכdi-bren barεri εn alaw harmful sכbstans dεm fכ go insay di bren tisu izi wan, we de mek nyuroinflameshכn εn nyurodijεnεreshכn bכku. di gap jכnkshכn bitwin nyuron dεm rili implεnt fכ di transmishכn fכ ilektrikal signal dεm εn mεtabolik kכdכnayshכn bitwin nyuron dεm. fכs tin dεm we di senesεnt sεl dεm de sekret kin disrupt di fכnshכn fכ di gap jכnkshכn dεm, we de afekt di sinkroniz aktiviti εn infכmeshכn transmishכn bitwin nyuron dεm.
(4) Efεkt dεm pan di maykro envayroment fכ nyural stεm sεl dεm
. di SASP fכktכ dεm we di senesεnt sεl dεm de sekret kin chenj di maykro envayroment fכ di nyural stεm sεl dεm, we de inhεbit dεn proliferashכn εn difrεns. sכm saytokכn dεm na SASP kin upregulate di εksprεshכn fכ sayklin-dipεndεnt kinase inhibito dεm, we de mek nyural stεm sεl dεm de arεst na spεsifi k stej dεm na di sεl saykl εn nכ ebul fכ כnda nכmal divεlכpmεnt εn difrεns. di inflammatory fכktכ dεm we di senesεnt sεl dεm de sekret kin infכlכ di difrεns dεyshכn fכ di nyural stεm sεl dεm bak, we de mek dεn difrεnt mכr to glial sεl dεm pas nyuron dεm, we de afekt nyural rigεnεreshכn εn ripa.
2. Impekt pan nyural stεm sεl maygrεshכn: nyural stεm sεl maygrεshכn na imכtant fכ dεn prכp lokalizεshכn εn fכnshכnal aktiviti insay di bren. sכm tin dεm we di senesεnt sεl dεm de kכl kin ambɔg di nyural stεm sεl dεm we de muv, we de mek dεn nכ muv to εria dεm we nid fכ ripa. di abnכmal εksprεshכn fכ di kεmokin dεm kin chenj di maygrεshכn dairekshכn fכ di nyural stεm sεl dεm, we de mek dεn nכ de rich di sayt we di injuri fכ ripa, we de mek di nεv sistεm in sεlf-ripa kapasiti de impεr.
Alzaima sik tritmɛnt strateji dɛm wae de tɔch di sɛl dɛm wae dɔn ol
(1) Sɛnolaytiks
. di mεkanism dεm fכ akshכn fכs inklud fכ indyuz senesεnt sεl apoptosis εn inhεbit senesεnt sεl anti-apoptotik signal path dεm. Dasatinib ɛn quercetin na di kɔmbaynshɔn dɛm we dɛn dɔn stɔdi pas ɔl naw fɔ senolytics. dasatinib kin inhεbit di כvaaktiv kinase signal path dεm na di senesεnt sεl dεm, we kεrεtin de εnhans di ifekt dεm we dasatinib de gi. we dεn yuz dεm togɛda, dεn kin sεlektivli indyuz apoptosis insay senesεnt sεl dεm εn ridyus dεn akyumyuleshכn na di bכdi.
. stכdi dεm fכnshכn se afta dεn gi dasatinib εn kεrεtin kכmbayn tεrapi to AD mכdel mays, di amoun כf Aβ plek dεm na di bren dכn dכn, nyuronal dεmεj dεm dכn rεdכks, εn spatial lanin εn mεmכri abiliti dεm impruv.
Figure 3 Sεlyul sεnesεns as kכmכpכnt fכ hεlty ol εn AD.
(2) Sεnesεns-asכsiet sekretri fεnotayp mכdulet dεm (Senomorphics) .
. sכm anti-inflammatory dכg dεm kin inhεbit di εksprεshכn εn sekreshכn fכ inflammatory fכktכ dεm na SASP, we de εliviet nyuroinflammatory. sכm sכm sכm mכlikul kכmpawnd dεm kin rεgεl di mεtabolik path dεm fכ di senesεnt sεl dεm, we de chenj di kכmכshכn fכ SASP fכ wik in damej ifekt dεm pan di sεl dεm we de rawnd.
. dis kin avכyd sכm pכtεnshal risk dεm we de asai wit senesεnt sεl kliarεns ejen dεm, lεk nכn spεsifi k damej to nכmal sεl dεm. fכ dat, senesεns-asכsiet sekretri fεnotayp mכdulet dεm de hכl brayt aplikεshכn prכspεkt dεm εn kin kכmכt as nyu tεrapi stratεji fכ AD.
Dɔn
di senesεnt sεl dεm de ple bכku pat dεm fכ di biginin εn di prכgreshכn fכ di Alzaima sik. tru mεkanism dεm lεk fכ indyuz nyuroinflameshכn, fכ protεkt nyurodijεnεreshכn, fכ altεr intasεlulyar kכmyunikeshn, εn fכ infכlכ di maykro envayroment fכ nyural stεm sεl dεm, senesεnt sεl dεm de εksayz di patכlayz prכsεs fכ AD. di tεrapi stratεji dεm we de tכk bכt di senesεnt sεl dεm, lεk di divεlכpmεnt fכ senesεnt sεl kliarεns ejen dεm εn senesεns-asכsiet sekretri fεnotayp mכdulet dεm, de gi nyu opshכn fכ di tritmεnt fכ AD.
Sos dɛn we dɛn pul
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