Cocer Peptides fɛ 
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BƐƐRƐ KUNNAFONIW NI FƐRƐW KUNNAFONIW BƐƐ MIN BƐ NI WEBSITE KAN NA, U BƐ KUNNAFONIW FƆLƆ DƆRƆN NI KALANSENW YE.
Fɛn minnu bɛ di nin siti in kan, olu dabɔra ɲininiw dɔrɔn kama in vitro. Sɛgɛsɛgɛli in vitro (latinkan na: *glasi kɔnɔ*, o kɔrɔ ye gilasi kɔnɔ) bɛ kɛ hadamaden farikolo kɔkan. Nin fura ninnu tɛ furaw ye, Ameriki ka dumuniko ni furako ɲɛmɔgɔso (FDA) ma sɔn u ma, wa u man kan ka kɛ ka furakɛli bana, bana walima bana si bali, k’a furakɛ, walima k’a furakɛ. A dagalen don kosɛbɛ sariya fɛ ka nin fɛn ninnu don hadamaden walima bagan farikolo la cogo o cogo.
Kuma bɛɛ lajɛlen
Nin barokun bɛ fɛɛrɛw sɛgɛsɛgɛ minnu bɛ kɛ sababu ye ka farikolokisɛ kɔrɔlenw dɛmɛ ka Alzheimer bana (AD) daminɛ ani ka taa ɲɛ. Alzheimer bana ye farikolojidɛsɛbana ye min ka teli ka sɔrɔ mɔgɔkɔrɔbaw de la fɔlɔ, a bɛ sɔrɔ hakiliɲagami dɔɔni dɔɔni fɛ ani kɛwalew dɛsɛ. Ni diɲɛ kɔnɔ mɔgɔw bɛ ka kɔrɔbaya, AD sɔrɔli bɛ ka caya san o san, o bɛ doni belebele da jamana ni denbayaw kan. Hali ni ɲɛtaa caman kɛra AD ɲininiw na, a sababu tigitigi ni a banakisɛ sɔrɔcogo ma jɛya hali bi. I n’a fɔ AD farati fɔlɔ dɔ, selilɛriw ka kɔrɔya ye jateminɛ kɛ ka taa a fɛ nin san laban ninnu na, a jɔyɔrɔ kosɔn AD banakisɛ sɔrɔli la. Kɔrɔyabanakisɛw dalajɛli farikolo la, o ni kɔrɔya bana suguya caman daminɛni ni u taabolo bɛ tali kɛ ɲɔgɔn na kosɛbɛ. Kɔnɔnatumu kɔrɔlenw jɔyɔrɔ ka bon AD banako taabolo la, wa u ka baarakɛcogo ɲɛfɔli nafa ka bon kosɛbɛ AD furakɛli kura labɛnni na.
Jaa 1. Alzheimer bana banakisɛfagalanw bɛ kɛ sababu ye ka kunsɛmɛbanakisɛw kɔrɔbaya. (a) Sugunɛbilenni kɔrɔlenw ni amiloyi sɔgɔlenw ni banakisɛfagalan tau cɛ jɛɲɔgɔnya jateminɛ. (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 BBB dafalenko tiɲɛnen AD kɔnɔ.
Kɔrɔya selilɛriw lajɛlen
(1) Kɔrɔya selilɛriw ɲɛfɔli n’u jogo
Kɔrɔya bɛ tali kɛ farikolokisɛw ka bonya minɛni na min tɛ se ka segin kɔ, u kɛlen kɔ ka tila-tila hakɛ dɔ la walima ni u kɛra degun suguya caman na (i n’a fɔ oksidan degun, ADN tiɲɛni, telomɛrɛw surunyali, a ɲɔgɔnnaw). Kɔnɔnatumu kɔrɔlenw bɛ fɛnɲɛnamafagalanw cogoya kɛrɛnkɛrɛnnenw jira, i n’a fɔ selilu hakɛ caya, u flakɛli, ani β-galactosidase (β-gal) baara caya, o min ye ɲɛnamaya taamasiɲɛ ye min bɛ kɛ ka caya walasa ka selilu kɔrɔlenw dɔn. Ka fara o kan, selilu kɔrɔlenw bɛ kinase inhibiteurs (i n’a fɔ p16INK4a ani p21Cip1) minnu bɛ tali kɛ siklin na, olu ka wulicogo jira, olu bɛ seliluw ka cycle progression bali, o bɛ kɛ sababu ye ka seliluw minɛ G1 fasa walima G2/M fasa la, o la, u bɛ tilali wɛrɛw bali.
Kɔrɔya selilɛriw dilanni fɛɛrɛw
1. Oksidan degun ni ADN tiɲɛni: Oksidan degun ye selilɛri kɔrɔbayali sababuba ye. Ni farikolo cogoya bɛnnen don, oksizɛni suguya minnu bɛ se ka kɛ (ROS) dilanni n’u bɔli selilu kɔnɔ, o bɛ balansi fangama kɔnɔ. Nka, ni mɔgɔ kɔrɔla walima ni bana dɔw bɛ a la, ni ROS bɔli cayara, o bɛ na ni ADN tiɲɛni ye. Ni ADN tiɲɛni bɛ dalajɛ fo ka se hakɛ dɔ ma, wa a tɛ se ka dilan ka ɲɛ, taamasiɲɛw sira caman bɛ baara kɛ, i n’a fɔ p53-p21 ani p16-Rb taamasiɲɛw siraw, o bɛ kɛ sababu ye ka seliluw bila ka don kɔrɔya cogo la. Alzheimer banabagatɔw ka kunkolo yɔrɔw la, oksidan degun hakɛ bɛ caya kosɛbɛ, o bɛ na ni ADN tiɲɛni caya ye senfagabana ni glial selilɛriw la, o min bɛ kɛ sababu ye ka selilɛriw kɔrɔbaya.
2. Telomere surunyali : Telomere ye ADN sinsinni ye min bɛ segin-ka-bɔ ɲɔgɔn na kolosinsinnanw labanw na minnu bɛ surunya dɔɔni dɔɔni ni selilɛri tilali ye. Ni telomɛrɛw surunyara fo ka se janya dɔ ma, u bɛ kɔrɔya taamasiɲɛw lawuli. Sɔgɔsɔgɔninjɛw la, telomɛrɛw surunyali bɛ tali kɛ kɔrɔya daminɛ na kosɛbɛ, o bɛ se ka senfagabana jirisunw yɛrɛ kurayali ni u danfara seko tiɲɛ, o la, a bɛ nɔ bila farikoloɲɛnajɛw yiriwali n’u baaracogo ɲuman na.
Kɔrɔyabanakisɛw ka baara kɛcogo Alzheimer bana na
(1) Induction de l’inflammation neuronale
1. Kɔrɔya-sɔgɔsɔgɔninjɛ-fenotipi (SASP) jɔyɔrɔ : Kɔrɔya-banakisɛw bɛ gundolafɛn kɛrɛnkɛrɛnnen dɔ jira min bɛ wele ko kɔrɔya-sɔgɔsɔgɔninjɛ fɛnɲɛnamafagalan (SASP). SASP bɛ kɛ ni sitokini suguya caman ye, kemikiniw, bonyafɛnw ani poroteyiziw, i n’a fɔ interleukin-6 (IL-6), interleukin-8 (IL-8), ani tumor necrosis factor-α (TNF-α). Alzheimer banabagatɔw ka kunsɛmɛ na, glial cellules senescentes ni neurones bɛ SASP factors caman bɔ, o bɛ se ka farikolo tangalanw lamini baara kɛ ani ka funu jaabi basigilenw lawuli. IL-6 ni TNF-α bɛ mikroglia baarakɛli sabati, o bɛ kɛ sababu ye u ka bɔ lafiya cogo la ka taa funu dɛmɛni cogo la, ka funu cɛmancɛlafɛn caman bɔ ani ka senfagabana juguya ka taa a fɛ. O funu basigilen in bɛ senfagabana tiɲɛ, ka sinankunya baara tiɲɛ, wa a bɛ na ni hakilijagabɔbaliya ye.
2. A bɛ nɔ bila glial cellules la : Astrocytes ni microglia kɔrɔbayali jɔyɔrɔ ka bon AD neuroinflammation na. Kɔrɔya astrocytes bɛ SASP fɛnw bɔ kɛnɛ kan minnu bɛ β-amyloïde (Aβ) farali ni a bilali sabati ka sɔrɔ k’a bɔli bali. Microglia kɔrɔbayali bɛ dɔ bɔ u seko la ka Aβ fagositɔsi, o bɛ Aβ plaques (banakisɛfagalanw) bɔli bali ka ɲɛ sugunɛ na. O nɔ na, u bɛ funufɛn caman bɔ, ka fɛn jugu dɔ lawuli min bɛ farikolo funu ni farikolojidɛsɛ juguya.
Jaa 2 Selulɛri kɔrɔya taamasiɲɛw bɛ caya hTau sogow hakili la minnu bɛ AD tauopathie modeli.
(2) Hakilila-jɔ-cogo ɲuman sabatili
1. Tiɲɛni tilennen don senfagabana la: Sitokini ni protéase dɔw minnu bɛ bɔ farikolokisɛ kɔrɔlenw fɛ, olu bɛ se ka senfagabana tiɲɛ k’a ɲɛsin u ma. Matrix metalloprotéinases (MMP) ye senescence-associé secretome (SASP) yɔrɔ dɔ ye, o bɛ se ka extracellular matrix ni neurotransmitter-related proteins tiɲɛ, ka senfagabana jɔcogo n’a baara tiɲɛ. ROS min bɛ sɔrɔ farikolokisɛ kɔrɔlenw fɛ, o fana bɛ se ka oksidan tiɲɛni kɛ senfagabana na, o bɛ na ni senfagabana apoptose ni saya ye. AD banabagatɔw ka kunsɛmɛ na, senfagabana kɔrɔya bɛ tali kɛ farikolokisɛw ka saya la kosɛbɛ, o bɛ se ka kɛ fɛnba dɔ ye min bɛ kɛ sababu ye ka hakiliɲagami bila mɔgɔ la.
2. Ɲɛgɛnɛsiraw tali bali: Ni farikolokisɛ kɔrɔlenw sɔrɔli fana bɛ se ka farikolojidɛsɛbanakisɛw dilanni, u bɔli ani u cili tiɲɛ. Funufɛnw bɛ se ka asetilkolini sɔrɔli bali, o ye farikolojidɛsɛ fura ye min nafa ka bon walasa ka hakili baara kɛcogo ɲuman sabati. Ka fara o kan, fɛn dɔw bɛ bɔ farikolokisɛ kɔrɔlenw fɛ, olu bɛ se ka nɔ bila farikolojidɛsɛbanakisɛfagalanw jiracogo n’u baara la, o bɛ na ni farikolojidɛsɛbanakisɛw taamasiɲɛw ye minnu tɛ bɛn, ka kumaɲɔgɔnya ni kunnafoniw baaracogo tiɲɛ ka taa a fɛ senfagabana ni ɲɔgɔn cɛ, wa o bɛ se ka hakiliɲagami bila mɔgɔ la.
(3) Yɛlɛma donna seliluw ni ɲɔgɔn cɛ kumaɲɔgɔnya la
1. Parakirini taamasiɲɛw kɛcogo jugu : Kɔnɔnatumu kɔrɔlenw bɛ kumaɲɔgɔnya kɛ ni u lamini farikolokisɛw ye parakirini taamasiɲɛw fɛ ni SASP fɛnw bɔli ye. O ko ninnu bɛ se ka nɔ bila sigiɲɔgɔnw ka seliluw baaracogo n’u ka siniɲɛsigi la, o bɛ na ni seliluw ni ɲɔgɔn cɛ kumaɲɔgɔnya sira tiɲɛ. AD banabagatɔw ka kunsɛmɛ na, SASP fɛn minnu bɛ bɔ ɲɛgɛnɛsira kɔrɔlenw fɛ, olu bɛ se ka nɔ bila senfagabana falenni na, u ka ɲɛnamaya la, ani u ka danfara la, ka sɔrɔ ka nɔ bila fana senfagabana jirisunw ka sigida fitininw na, ka u caya ni u danfara bali, o la, u bɛ nɔ bila senfagabana seginni ni u dilancogo la.
2.Seliluw ni ɲɔgɔn cɛ jɛɲɔgɔnyaw tiɲɛni : Kɔnɔnatumu kɔrɔlenw fana bɛ se ka seliluw ni ɲɔgɔn cɛ jɛɲɔgɔnyaw tiɲɛ, i n’a fɔ ɲɔgɔndan sirilenw ani ɲɔgɔndanw. Joli-sɔgɔsɔgɔninjɛ la, endoteliyali selilɛriw kɔrɔbayali bɛ na ni ɲɔgɔndan sirilenw farikolojɔlifɛnw jirali dɔgɔyali ye, o bɛ dɔ fara joli-sɔgɔsɔgɔninjɛ balilan ka doncogo kan ani ka a to fɛn juguw ka don kunsɛmɛ na nɔgɔya la, o bɛ farikolo funu ni farikolojidɛsɛ juguya. Gap junctions (yɔrɔ) minnu bɛ senfagabana ni ɲɔgɔn cɛ, olu nafa ka bon kosɛbɛ kuran taamasiɲɛw lasecogo la ani farikoloɲɛnajɛ jɛɲɔgɔnya la senfagabana ni ɲɔgɔn cɛ. Fɛn minnu bɛ bɔ farikolokisɛ kɔrɔlenw fɛ, olu bɛ se ka gap junctions baara tiɲɛ, ka nɔ bila baara kɛcogo la min bɛ kɛ ɲɔgɔn fɛ ani kunnafoni cicogo la senfagabana ni ɲɔgɔn cɛ.
(4) A bɛ nɔ minnu bila senfagabana jirisunw ka sigida fitininw na
1. Senfagabana jirisunw caya ni u danfara balili : Senfagabana jirisunw bɛ bagan balikuw ka hakili la, wa se bɛ u ye ka u yɛrɛ kuraya ani ka danfara don u ni ɲɔgɔn cɛ ka kɛ senfagabana, astrocytes ani oligodendrocytes ye. SASP fɛnw minnu bɛ bɔ mɔgɔkɔrɔbaw fɛ, olu bɛ se ka senfagabana jirisunw ka sigida fitinin caman Changer, ka u caya ni u danfara bali. Sitokini dɔw bɛ SASP kɔnɔ, olu bɛ se ka siklin-dependant kinase inhibiteurs (siklin-dependant kinase inhibiteurs) jiracogo kɔrɔta, o bɛ kɛ sababu ye ka senfagabana sɔgɔsɔgɔninjɛw minɛ selilu sɛgɛsɛgɛli waati kɛrɛnkɛrɛnnenw na ani u tɛ se ka tilacogo ni danfara kɛcogo ɲuman kɛ. Funufɛn minnu bɛ bɔ mɔgɔkɔrɔbaw fɛ, olu fana bɛ se ka nɔ bila senfagabana jirisunw ka danfara siratigɛ la, o bɛ kɛ sababu ye u ka danfara ka caya ka kɛ glial selilɛriw ye sanni ka kɛ senfagabana ye, o bɛ nɔ bila senfagabana seginni ni u dilancogo la.
2. Kɔnɔnafili min bɛ sɔrɔ senfagabana jirisunw jiginni na : Senfagabana jirisunw jiginni nafa ka bon kosɛbɛ walasa u sigiyɔrɔ ka ɲi ani u ka baara kɛcogo ɲuman na hakili kɔnɔ. Fɛn dɔw bɛ bɔ farikolokisɛ kɔrɔlenw fɛ, olu bɛ se ka farikolojidɛsɛbanakisɛw ka jiginni bali, o bɛ u bali ka taa yɔrɔw la minnu ka kan ka dilan. Kemokiniw jiracogo jugu bɛ se ka farikolojidɛsɛbanakisɛw ka jiginni sira Changer, ka u bali ka se joginni yɔrɔ la walasa ka u dilan, o la, u bɛ se ka farikolojidɛsɛ yɛrɛdilan seko tiɲɛ.
Alzheimer bana furakɛli fɛɛrɛw minnu bɛ mɔgɔkɔrɔbaw laɲini
(1) Senolitikiw (Senolytics).
1. A kɛcogo : Senolitikiw ye fɛnɲɛnamafagalan suguya dɔ ye min bɛ se ka kɔrɔyabanakisɛw bɔ yen ka sugandi. U ka baara kɛcogo fɔlɔ ye ka selilu kɔrɔlenw ka apoptose (banakisɛfagalan kɔrɔlenw ka apoptose) bila mɔgɔ la ani ka selilu kɔrɔlenw ka apoptose kɛlɛli taamasiɲɛw siraw bali. Dasatinib ni quercetin ye senolytiques faralen ɲɔgɔn kan minnu sɛgɛsɛgɛra kosɛbɛ sisan. Dasatinibi bɛ se ka kinase taamasiɲɛw siraw bali minnu bɛ baara kɛ kojugu farikolokisɛ kɔrɔlenw na, ka sɔrɔ quercetin bɛ dasatinibi nɔw bonya. Ni u kɛra ɲɔgɔn fɛ, u bɛ se ka sugandili kɛ ka apoptose (banakisɛfagalanw fagali) bila mɔgɔkɔrɔbaw la ani ka dɔ bɔ u dalajɛli la farikolo la.
2.Ɲɛtaa baganw ka kɔrɔbɔliw ni kɛnɛyaso kalanw na : Baganw ka kɔrɔbɔliw la, AD modɛli sogow furakɛli ni selilu kɔrɔlenw bɔli furaw ye, o ye dɔ bɔ kosɛbɛ kɔrɔyabanakisɛw hakɛ la kunsɛmɛ na, ka farikolojidɛsɛ hakɛ dɔgɔya, ka hakili baara ɲɛ. Kɔlɔsiliw y’a jira ko dasatinibi ni quercetin faralen ɲɔgɔn kan furakɛli kɛlen kɔfɛ AD modɛli sogow la, Aβ plaques hakɛ bɛ dɔgɔya kunsɛmɛ na, senfagabana tiɲɛni bɛ dɔgɔya, ani yɔrɔ kalanni ni hakilijagabɔ sekow bɛ ɲɛ.
Jaa 3 Kɔnɔnatumuw ka kɔrɔya i n’a fɔ kɔrɔya kɛnɛman ni AD yɔrɔ dɔ.
(2) Senescence-associé secretoire phenotype modulateurs (Senomorphics) .
1. Baara kɛcogo : Senomorfikiw laɲini ye ka SASP fɛnw bɔli labɛn farikolokisɛ kɔrɔlenw fɛ, ka dɔ bɔ u nɔ juguw la farikolokisɛ lamini na. Fura dɔw bɛ se ka funufɛnw jirali ni u bɔli bali SASP kɔnɔ, ka farikolo funu nɔgɔya. Fɛnɲɛnɛma misɛnnin dɔw bɛ se ka farikolokisɛ kɔrɔlenw ka farikoloɲɛnajɛ siraw labɛn, ka SASP kɛcogo Changer walasa k’a ka tiɲɛniw dɔgɔya farikolokisɛw lamini na.
. O bɛ se ka kɛ sababu ye ka farati dɔw bali minnu bɛ se ka sɔrɔ farikolokisɛ kɔrɔlenw bɔli furaw fɛ, i n’a fɔ tiɲɛni kɛrɛnkɛrɛnnen tɛ farikolokisɛw la minnu ka kɛnɛ. O la, senescence-associé secretoire phenotype modulateurs bɛ baarakɛcogo caman minɛ, wa u bɛ se ka bɔ kɛnɛ kan i n’a fɔ furakɛli fɛɛrɛ kura AD la.
Kuncɛli
Kɔnɔnatumu kɔrɔlenw jɔyɔrɔ ka bon kosɛbɛ Alzheimer bana daminɛni ni a taabolo la. Fɛɛrɛw sababu fɛ i n’a fɔ ka farikolo funu bila mɔgɔ la, ka farikolojidɛsɛ sabati, ka seliluw ni ɲɔgɔn cɛ kumaɲɔgɔnya caman cili, ani ka nɔ bila senfagabana jirisunw ka sigida fitininw na, farikolokisɛ kɔrɔlenw bɛ AD bana taabolo juguya. Furakɛli fɛɛrɛ minnu bɛ kɛ ka ɲɛsin mɔgɔkɔrɔbaw ma, i n’a fɔ kɔrɔyabanakisɛw bɔli furaw dilanni ani kɔrɔya ni kɔrɔya ni gundolafɛnw sɛgɛsɛgɛlikɛlanw, olu bɛ fɛɛrɛ kuraw di AD furakɛli ma.
Sosow (Sɔrɔyɔrɔw).
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