Na Cocer Peptides 
1 mois eleki
BA ARTICLES MPE BA INFORMATIONS NIONSO YA PRODUIT OYO EPESAMI NA SITE OYO EZALI KAKA MPO NA KOPANZI BA INFORMATIONS MPE MPO NA NTINA YA KOTEYA.
Biloko oyo epesami na site oyo ezali kaka mpo na bolukiluki na kati ya in vitro. Bolukiluki in vitro (na latin: *na verre*, elingi koloba na biloko ya verre) esalemaka libanda ya nzoto ya moto. Biloko yango ezali bankisi te, endimami te na ebongiseli moko (FDA) ya États-Unis oyo etalelaka bilei mpe bankisi, mpe esengeli te kosalela yango mpo na kopekisa, kosalisa to kobikisa maladi, maladi to maladi nyonso. Mibeko epekisi mpenza kokotisa biloko yango na nzoto ya moto to ya nyama na lolenge nyonso.
Botali ya mozindo
Lisolo oyo ezali kotalela ndenge oyo baselile oyo ekómi mibange esalaka ete maladi ya Alzheimer (TDA) ebanda mpe ekóma makasi. Maladi ya Alzheimer ezali maladi oyo emonanaka mingi na misisa ya bɔɔngɔ oyo ekómelaka libosoliboso mibange, oyo emonanaka na kozanga mayele ya kososola mokemoke mpe kozanga bizaleli. Wana motángo ya bato na mokili mobimba ezali kokóma mibange, motángo ya bato oyo bazali na maladi ya AD ezali se kobakisama mbula na mbula, mpe yango ezali kotya mokumba monene likoló na bato mpe mabota. Atako bokoli monene esalemi na bolukiluki ya AD, etiologie ya sikisiki mpe pathogénèse etikali polele te. Lokola moko ya makambo ya libosoliboso oyo ekoki kobimisa AD, kokóma mobange ya baselile ezwaki likebi mingi na bambula oyo euti koleka mpo na mokumba na yango na pathogénèse ya AD. Koyangana ya baselile oyo ekómi mibange na nzoto ezali na boyokani makasi na ebandeli mpe bokoli ya bamaladi ndenge na ndenge oyo euti na mbula. Ba cellules senescentes ezali na rôle ya ntina mingi na processus pathologique ya AD, mpe ko elucider ba mécanismes na yango ya action ezali na signification munene pona ko développer ba traitements ya sika ya AD.
Figure 1. Ba proteines pathogènes ya maladie ya Alzheimer esalisaka na senescence ya ba cellules ya cerveau. (a) Botali ya mozindo ya boyokani kati na baselile ya bɔɔngɔ́ oyo ekómi mibange na baplakɛ ya amyloïde mpe tau oyo epesaka maladi. (b–e) Detailed view of each respective cell type and senescence-associated features reported in the literature: (b) neuron, (c) microglia, (d) oligodendrocyte/oligodendrocyte precursor cell, (e) astrocyte, and (f) blood-brain barrier (BBB) featuring endothelial cells, pericytes, and astrocytes, demonstrating compromise intégrité ya BBB na AD.
Botali ya mozindo ya ba Cellules Senescentes
(1) Ndimbola mpe bizaleli ya baselile oyo ekómi mibange
Senescence elakisi bokangami ya bokoli ya baselile oyo ekoki kobongwana te sima ya kosala motango moko boye ya bokabwani to kozala na ba facteurs ya stress ndenge na ndenge (lokola stress oxidatif, kobebisa ADN, kokita ya ba télomères, mpe bongo na bongo). Ba cellules senescentes elakisaka ba caractéristiques phénotypiques unique, na kati na yango volume ya cellule oyo emati, plat, mpe activité ya β-galactosidase (β-gal) oyo emati, oyo ezali marqueur biologique oyo basalelaka mingi pona koyeba ba cellules senescentes. En plus, ba cellules senescentes elakisaka upregulation ya ba inhibiteurs ya kinase dépendants ya cycline (lokola p16INK4a na p21Cip1), oyo e pekisaka progression ya cycle cellulaire, esalaka que ba cellules ekangama na phase G1 to phase G2/M mpe na yango epekisaka division mosusu.
Mecanismes ya Formation ya ba Cellules Senescentes
1. Stress oxidatif mpe kobebisa ADN: Stress oxidatif ezali inducteur ya ntina ya senescence cellulaire. Na ba conditions physiologiques normales, production mpe dégagement ya ba espèces ya oxygène réactif (ROS) na kati ya ba cellules ezali na équilibre dynamique. Kasi, soki moto akómi mobange to soki azali na makambo mosusu ya maladi, kobimisama mingi ya ROS esalaka ete ADN ebeba. Ntango kobebisama ya ADN esanganaka na ndenge moko boye mpe ekoki kobongisama malamu te, molɔngɔ ya banzela ya kopesa bilembo efungolaka, na ndakisa banzela ya kopesa bilembo p53-p21 mpe p16-Rb, mpe yango etindaka baselile ekɔta na ezalela ya kokóma mibange. Na misisa ya bɔɔngɔ oyo euti na bato ya maladi ya Alzheimer, nivo ya stress oxidatif emati mpenza, mpe yango esalaka ete ADN ebeba mingi na ba neurones mpe na baselile ya glial, mpe yango esalaka ete baselile ekóma mibange.
2. Kokómisa ba télomères mokuse: Ba télomères ezali ba séquences ya ADN oyo ezongaka mbala na mbala na nsuka ya ba chromosomes oyo ekómaka mokuse mokemoke ntango baselile ekabwani. Ntango ba télomères ekómi mokuse tii na bolai moko boye, ebimisaka bilembo ya kokóma mibange. Na ba cellules souches neuronale, kokoma mokuse ya ba télomères ezali na boyokani makasi na ebandeli ya senescence, oyo ekoki kobebisa makoki ya komizongisa sika mpe ya différenciation ya ba cellules souches neuronale, na yango kozala na bopusi na bokoli mpe mosala ya système nerveux normal.
Mecanisme ya action ya ba cellules senescentes na maladie ya Alzheimer
(1) Induction ya Neuroinflammation
1. Role ya phénotype sécrétoire associé na sénescence (SASP): Ba cellules senescentes elakisaka phénotype sécrétoire unique oyo eyebani na kombo ya phénotype sécrétoire associé na sénescence (SASP). SASP ezali na ba cytokines, ba chemokines, ba facteurs de croissance, mpe ba proteases ndenge na ndenge, lokola interleukin-6 (IL-6), interleukin-8 (IL-8), mpe facteur ya nécrose tumeur-α (TNF-α). Na misisa ya bɔɔngɔ ya bato ya maladi ya Alzheimer, baselile ya gliale mpe ba neurones oyo ekómi mibange ebimisaka ebele ya makambo ya SASP, oyo ekoki kosala ete baselile ya nzoto oyo ezali zingazinga na yango esala mosala mpe ebimisa biyano ya kozoka oyo eumelaka. IL-6 mpe TNF-α esalisaka microglia esala mosala, mpe esalaka ete elongwa na ezalela ya kimia kino na ezalela ya pro-inflammatoire, ebimisaka ba médiateurs inflammatoires mingi mpe ebakisaka lisusu neuroinflammation. Environnement inflammatoire oyo ewumeli ebebisaka ba neurones, ebebisaka fonctionnement synaptique, mpe ememaka na dysfonctionnement cognitif.
2. Effet na ba cellules gliales: Kokóma mobange ya ba astrocytes mpe microglia ezali na rôle ya ntina mingi na neuroinflammation ya AD. Ba astrocytes oyo ekómi mibange ebimisaka ba facteurs SASP oyo esalisaka agrégation mpe dépôt ya β-amyloïde (Aβ) tout en inhibition ya dégagement na yango. Kokóma mobange ya ba microglia ekitisaka makoki na yango ya ko phagocytose Aβ, mpe yango epekisaka ete ba plaques ya Aβ elongolama malamu na bɔɔngɔ. Na esika na yango, ebimisaka biloko mingi oyo epelisaka nzoto, mpe ebimisaka zingazinga ya mabe oyo ebakisaka kovimba ya misisa ya bɔɔngɔ mpe kobeba ya misisa ya bɔɔngɔ.
Figure 2 Ba marqueurs ya senescence cellulaire emati na cerveau ya ba souris hTau oyo ezo modeler tauopathie ya AD.
(2) Kotombola maladi ya misisa ya bɔɔngɔ
1. Kobebisa ba neurones mbala moko: Ba cytokines mpe ba proteases mosusu oyo ebimisamaka na baselile oyo ekómi mibange ekoki kobebisa mbala moko ba neurones. Ba métalloprotéinases matrice (MMP) ezali moko ya biloko oyo esalaka secrétome associé na senescence (SASP), oyo ekoki kobebisa matrice extracellulaire mpe ba protéines oyo etali neurotransmetteur, mpe kobebisa structure mpe fonctionnement ya ba neurones. ROS oyo ebimisami na baselile oyo ekómi mibange ekoki mpe kobebisa ba neurones na nzela ya oxidation, mpe yango ekoki komema na apoptose neuronale mpe liwa. Na misisa ya bɔɔngɔ ya bato ya maladi ya AD, kokóma mibange ya baselile ezali na boyokani makasi na liwa ya baselile, oyo ekoki kozala moko ya makambo ya ntina oyo esalaka ete bato báyeba malamu te.
2. Kopekisa bopanzani ya ba neurotransmetteurs: Kozala ya ba cellules senescentes ekoki mpe kobebisa synthèse, liberation mpe transmission ya ba neurotransmetteurs. Ba facteurs inflammatoires ekoki kopekisa synthèse ya acétylcholine, neurotransmetteur oyo ezali na ntina mingi mpo na kobatela fonctionnement cognitif normal. Longola yango, makambo mosusu oyo baselile oyo ekómi mibange ebimisaka ekoki kozala na bopusi likoló na ndenge oyo ba récepteurs neurotransmetteurs emonisaka mpe mosala na yango, mpe yango ekoki komema na kopesa bilembo na ba neurotransmetteurs oyo ezali malamu te, mpe yango ebebisaka lisusu boyokani mpe mosala ya nsango kati na ba neurones, mpe na ndenge yango, ekoki kosala ete bato báyeba malamu te.
(3) Mbongwana na boyokani kati na baselile
1. Signalisation paracrine anormale : Ba cellules senescentes e communiquer na ba cellules ya zinga zinga na nzela ya signalisation paracrine na ko sécréter ba facteurs SASP. Makambo yango ekoki kozala na bopusi likoló na mosala mpe nsuka ya baselile oyo ezali pembenipembeni, mpe yango ekoki komema na kobebisama ya réseau ya boyokani kati na baselile. Na tissus ya cerveau ya ba malades ya AD, ba facteurs SASP oyo ebimisamaka na ba cellules gliales senescentes ekoki kozala na influence na croissance neuronale, survie, mpe différenciation, tout en influencer na microenvironnement ya ba cellules souches neuronale, kopekisa prolifération mpe différenciation na yango, na yango ko affecter ba processus ya régénération neuronale mpe ya réparation.
2.Kobebisa ba connexions intercellulaires : Ba cellules senescentes ekoki pe ko déranger ba structures ya connexion intercellulaire, lokola ba jonctions serrées na ba jonctions ya espace. Na kati ya eloko oyo epekisaka makila mpe bɔɔngɔ, kokóma mibange ya baselile ya endothélium ememaka na kokitisa expression ya baproteini ya jonction serrée, ebakisaka perméabilité ya barrière makila-bɔɔngɔ mpe epesaka nzela na biloko ya mabe ekɔta na pɛtɛɛ nyonso na misisa ya bɔɔngɔ, mpe yango ebakisaka kovimba ya misisa ya bɔɔngɔ mpe kobeba ya misisa ya bɔɔngɔ. Ba jonctions ya ba espaces entre ba neurones ezali cruciale pona transmission ya ba signaux électriques pe coordination métabolique entre ba neurones. Makambo oyo baselile oyo ekómi mibange ebimisaka ekoki kobebisa mosala ya ba jonctions ya ba espaces, mpe yango ekoki kosala ete ba activités synchronisées mpe transmission ya information entre ba neurones.
(4) Effet na microenvironnement ya ba cellules souches neuronale
1. Kopekisa bopanzani mpe bokeseni ya ba cellules souches neuronale: Ba cellules souches neuronale ezali na bɔɔngɔ ya banyama oyo ememaka mabɛlɛ oyo ekómi mikóló mpe ezali na likoki ya komizongisa sika mpe kokesana na ba neurones, ba astrocytes mpe ba oligodendrocytes. Ba facteurs SASP oyo ebimisamaka na ba cellules senescentes ekoki kobongola microenvironnement ya ba cellules souches neuronale, kopekisa prolifération mpe différenciation na yango. Ba cytokines mosusu na SASP ekoki ko upregulate expression ya ba inhibiteurs ya kinase dépendants ya cycline, kosala que ba cellules souches neuronale ekangama na ba étapes spécifiques ya cycle cellulaire mpe ekoki te ko subir division mpe différenciation normale. Ba facteurs inflammatoires oyo ebimisamaka na ba cellules senescentes ekoki mpe kozala na influence na direction ya différenciation ya ba cellules souches neuronale, kosala que e différencier mingi na ba cellules gliale na esika ya ba neurones, na yango e affecter regeneration mpe réparation ya neuronale.
2. Impact na migration ya ba cellules souches neuronale : Migration ya ba cellules souches neuronale ezali critique mpo na localisation na bango propre mpe activité fonctionnelle na kati ya cerveau. Makambo mosusu oyo baselile oyo ekómi mibange ebimisaka ekoki kopekisa baselile ya moboko ya misisa ya bɔɔngɔ ekende, mpe yango epekisaka yango ekende na bisika oyo esengeli kobongisama. Expression abnormale ya ba chemokines ekoki kobongola direction ya migration ya ba cellules souches neuronale, kopekisa yango ekoma na esika oyo ezokaki mpo na kobongisama, na yango kobebisa makoki ya système nerveux ya komibongisa.
Ba stratégies ya traitement ya maladie ya Alzheimer oyo etali ba cellules senescentes
(1) Ba sénolytiques
1. Mecanisme ya action: Ba sénolytiques ezali classe ya ba composés oyo ekoki ko sélectivement ko éliminer ba cellules senescentes. Ba mécanismes na bango ya action ezali libosoliboso ko induire apoptose ya ba cellules senescentes mpe kopekisa ba voies ya signalisation anti-apoptotique ya ba cellules senescentes. Dasatinib mpe quercetine ezali sikawa masangani ya ba sénolytiques oyo bayekolaka mingi. Dasatinib ekoki kopekisa ba voies ya signalisation ya kinase suractivée na ba cellules senescentes, alors que quercétine ematisaka ba effets ya dasatinib. Soki basaleli yango esika moko, bakoki kopona kosala ete baselile oyo ekómi mibange ekóma apoptose mpe kokitisa koyanganisa yango na nzoto.
2.Progrès na ba expériences ya nyama mpe ba études cliniques: Na ba expériences ya ba nyama, traitement ya ba souris modèle AD na ba agents ya dégagement ya ba cellules senescentes ekitisaki makasi motango ya ba cellules senescentes na cerveau, ekitisaki niveau ya neuroinflammation, mpe ebongisi fonctionnement cognitif. Ba études emonisaki que sima ya kopesa traitement combiné ya dasatinib na quercétine na ba souris modèle AD, quantité ya ba plaques Aβ na cerveau ekiti, ba dégâts ya ba neurones ekitisami, mpe makoki ya koyekola na esika ya bokundoli ebongwani.
Figure 3 Senescence cellulaire lokola composante ya vieillissement ya santé mpe AD.
(2) Ba modulateurs ya phénotype secrétaire associés na sénescence (Senomorphics) .
1. Mecanisme ya action : Ba sénomorphiques ezali na tina ya ko réguler sécrétion ya ba facteurs SASP na ba cellules senescentes, ko réduire ba effets mabe na yango na ba cellules ya zinga zinga. Ba kisi misusu ya anti-inflammatoire ekoki kopekisa expression mpe sécrétion ya ba facteurs inflammatoires na SASP, ko soulager neuroinflammation. Ba composés mosusu ya ba molécules ya mike ekoki ko réguler ba voies métaboliques ya ba cellules senescentes, ko changer composition ya SASP pona ko lembisa ba effets na yango ya mabe na ba cellules ya zinga zinga.
. Yango ekoki koboya mwa makama oyo ekoki kobima na biloko oyo epɛtolaka baselile oyo ekómi mibange, na ndakisa kobebisa baselile oyo ezali malamu te. Na yango, ba modulateurs ya phénotype secrétaire associés na senescence esimbaka ba perspectives ya application ya large mpe ekoki kobima lokola stratégie thérapeutique ya sika mpo na AD.
Maloba ya nsuka
Ba cellules senescentes esalaka rôle ebele na début mpe progression ya maladie ya Alzheimer. Na nzela ya ba mécanismes lokola ko induire neuroinflammation, ko promouvoir neurodégénérescence, ko changer communication intercellulaire, mpe ko influencer microenvironnement ya ba cellules souches neuronale, ba cellules senescentes e aggraver processus pathologique ya AD. Ba stratégies thérapeutiques oyo etali ba cellules senescentes, lokola développement ya ba agents ya dégagement ya ba cellules senescentes mpe ba modulateurs ya phénotype sécrétaire associés na senescence, epesaka ba options ya sika pona traitement ya AD.
Maziba oyo euti na yango
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