SS31 miligaramu 50

▎ SS-31 Jatebɔcogo

▎ SS-31 Sɛgɛsɛgɛli

SS-31 ka ɲininiw kɛcogo ye mun ye?

SS-31 ɲinini kɔkankow bɔra faamuyaliba la mitokondriyaw ka baarakɛbaliya kan ani furakɛli fɛɛrɛ minnu bɛ yen, olu dan ye. Mitokondriyaw nafa ka bon kosɛbɛ selilɛriw ka baara ni u ka baara la, wa u baarakɛbaliya bɛ tali kɛ bana suguya caman daminɛni n’u ka taa ɲɛ, i n’a fɔ sugunɛbana, farikolojidɛsɛ, ani dusukun tantanni. O cogoyaw la, fɛn dɔw bɛ bɔ mitokondriyaw ka biyojenizi la, u cogoya la, u kɛcogo la, ani fɛn caman Changements dynamique la, o bɛ kɛ sababu ye ka mitokondriyaw kɛ furakɛli laɲini nafama ye. Hali ni fura caman bɛ yen minnu ɲɛsinnen bɛ mitokondriyaw ma — NAD+ faralen ɲɔgɔn kan i n’a fɔ nikotinamidi mononukiliyɔtidi (NMN), lakanani furakisɛ min ɲɛsinnen bɛ mitokondriyaw ma MitoQ, ani farikolo tangalan coenzyme Q10 — laadala furaw bɛ dan sigi kɛnɛyaso la ka a sababu kɛ mitokondriyaw tali man ɲi walima baga caman. O de kosɔn, a ka kan kosɛbɛ ka furakɛlicogo ɲumanw labɛn, minnu ɲɛsinnen bɛ u ma.

Dusukun tantanni min bɛ sɔrɔ degun fɛ, o bɛ dusukun tantanni sababu fɔlɔ dɔ jira diɲɛ kɔnɔ, a banakisɛfagalanw ni mitokondriyaw baarakɛbaliya ni dusukun tantanni cɛmancɛ fibrose bɛ tali kɛ ɲɔgɔn na kosɛbɛ. Furakɛli fɛɛrɛ ɲumanw dɔnni nafa ka bon kosɛbɛ walasa ka banabagatɔw ka sɔrɔw ɲɛ. O hukumu kɔnɔ, ɲininikɛlaw ye SS-31 labɛn, n’o ye farikolo tangalan kura ye min ɲɛsinnen bɛ mitokondriyaw ma, walasa ka furakɛli magow ɲɛnabɔ banaw la minnu bɛ sɔrɔ mitokondriyaw ka baarakɛbaliya fɛ. A bɛ baara kɛ kɛrɛnkɛrɛnnenya la mitokondriyaw kɔnɔna na, ka mitokondriyaw jɔcogo n’u baara sabati ka sɔrɔ ka oksidan degun dɔgɔya, o bɛ nafa jira bana caman misaliw la.

SS-31 ka baarakɛcogo ye mun ye?

Mitokondriyaw ka baarakɛcogo ɲɛnabɔli

A ni karidiyolipini ka jɛɲɔgɔnya : Elamipretide bɛ mitokondriyaw kɔkanna tigɛ ka a siri karidiyolipini na. Kardiolipini ye fosifolipidi yɔrɔ koloma ye min bɛ mitokondriyaw kɔnɔna na, a jɔyɔrɔ ka bon kosɛbɛ mitokondriyaw jɔcogo n’u baara sabatili la. O jɛɲɔgɔnya in sababu fɛ, Elamipretide bɛ mitokondriyaw ka biyoɛnerji ni u cogoya ɲɛ. Nin wale in bɛ a yɛrɛ jira i n’a fɔ mitokondriyaw ka baara caya teliya la jirisunw na minnu fanga ka bon kosɛbɛ, kɛrɛnkɛrɛnnenya la farikolokisɛ minnu bɛ bɔ banabagatɔw la minnu bɛ ni Barth ka bana ye ani denmisɛnw ka dusukunnabana ciyɛntalen ^wɛrɛw.

Membrane farikolo cogoya caman caman cili : Mitchell W ka ɲininiw y’a jira ko Elamipretide bɛ baara kɛ ni lipid bilayer ye, ka mitokondriyaw farikolo cogoyaw sɛmɛntiya, kɛrɛnkɛrɛnnenya la electrostatic properties minnu bɛ membrane interface la. O pepitiri in bɛ jɛnsɛn ka taa membrane interface region la ni affinité ni binding density ye min bɛ tali kɛ surface charge la. Hali n’a tɛ lamellar bilayer basigibaliya ni sirili hakɛ caman ye, a bɛ saturation changements bila lipid stacking la, o bɛ nɔ bila mitochondrial membrane baara ^la.

Jaa 1 Fɛn minnu bɛ dusukun fanga sɔrɔli ni a ɲinini nɔ bila ^{[1] .}.

Nɛrɛmuguma lakanani

Hakilila baara sabatili : Sosow ka hakilijagabɔbaliya modɛli dɔ la, min bɛ kɛ ni lipopolisaccharide (LPS) ye, Elamipretide furakɛli ye kalan ni hakilijagabɔ sekow ɲɛ kosɛbɛ Morisi jibɔlan (MWM) la ani yɔrɔ siran sɛgɛsɛgɛliw la. O ɲɛtaa nɔ in bɛ se ka kɛ sababu ye ka a ka mitokondriyaw ka baara lakanani, ka oksidan degun dɔgɔya, ka taamasiɲɛw sira min bɛ bɔ hakili la (BDNF) labɛn, ani ka sinankunya jɔcogo gɛlɛya bonya. LPS furakɛli ye mitokondriyaw ka baarakɛbaliya, oksidan degun, funu, senfagabana apoptose, ani dendɛrɛsi kɔkolo bɔnɛ bila soso ka hipokampus la, ka sɔrɔ Elamipretide ye o joginw nɔgɔya, o b’a jira ko se bɛ se ka opereli kɔfɛ hakiliɲagami (PND) ^bali.

Senfagabana ka apoptose balili : Kɔkolo joginni (SCI) sɛgɛsɛgɛliw la, Elamipretide bɛ baarakɛcogo kɛnɛyali sabati ni a bɛ piroptosis bali, ka otofaji fanga bonya, ani ka lizozomi membrane perméabilité (LMP) dɔgɔya. A bɛ otofaji fanga bonya ni cPLA2 fosforilasi bali ye ka sɔrɔ ka piroptosi ni LMP nɔgɔya. O la, Elamipretide jɔyɔrɔ ka bon farikolo joginw dilancogo la, a kɛtɔ ka selilɛriw ka taabolo caman ɲɛnabɔ, ka senfagabana apoptose dɔgɔya, ani ka senfagabana baarakɛcogo kɛnɛya ^sabati.

Jaa 2 Elamipretide (SS-31) ye oksidan degun ni funu jaabi min bɛ sɔrɔ LPS fɛ sosow ka hipokampus la, o dɔgɔya. a Oksizɛni suguya min bɛ se ka kɛ (ROS) hakɛ, b malondialdehyde (MDA) hakɛ, ani c superoxide dismutase (SOD) baarakɛcogo ^{[3] .}.

SS-31 baarakɛcogo ye mun ye?

Hakilila-jɔ-banaw

Ɲɛkisɛw furakɛli : Ɲɛkisɛw ka ɲɛnamini (TON) bɛ se ka kɛ sababu ye ka ɲɛnayeli bɔnɛ kudayi ka a sababu kɛ ɲɛnamini sɔgɔsɔgɔninjɛ ye min tɛ ye. Kɔlɔsiliw ye SS-31 ni tumor necrosis factor (TNF) inhibitor etanercept faralen ɲɔgɔn kan, o bɛ se ka ɲɛda lakanani nɔw sɛgɛsɛgɛ ɲɛda ɲɛgɛnɛsira jogin kɔfɛ. Tse BC ka sɛgɛsɛgɛli min kɛra ni sosow ka TON modɛli ye min bɛ kɛ ni ultrasound ye (SI-TON), o y’a jira ko SS-31 pikiri kɛli ɲɛda la ni etanercept ni SS-31 pikiri kɛra farikolo jukɔrɔ, o ye dɔ fara kosɛbɛ RGC ka ɲɛnamaya kan ni 21% ye (p < 0,01) ni i ye a suma ni ɲɛkisɛw ye minnu furakɛra ni fositɛri tampon ye (PBS). Etanercept ni SS-31 pikiri faralen ɲɔgɔn kan farikolo jukɔrɔ, o ye dɔ fara RGC ka ɲɛnamaya kan ni 11% ye (p < 0,05) ni i ye a suma ni a kunbɛnbagaw ye; etanɛrisɛti dɔrɔn pikiri fari jukɔrɔ, o ye dɔ fara RGC ka ɲɛnamaya kan ni 20% ye (p < 0,01) ni i ye a suma ni a kunbɛnbagaw ye; SS-31 pikiri kɛli farikolo jukɔrɔ dɔrɔn, o ye dɔ fara RGC ka ɲɛnamaya kan ni 17% ye ni i ye a suma ni kɔrɔsili kulu ye (p < 0,01). Nin sɔrɔlen ninnu b’a jira ko SS-31 bɛ lakanani kɛ RGCw la ɲɛnaminibana furakɛli la, o la, a bɛ ɲɛnayeli ɲɛ TON banabagatɔw ^la.

Fɛɛrɛ sɔrɔli α-Synuclein-Related Neurodegenerative Diseases: Parkinson ka bana ni a ni a ɲɔgɔnna synucleinopathies bɛ tali kɛ ɲɔgɔn na kosɛbɛ ni α-synuclein ka membrane sirili ni a dalajɛcogo ye. Stefaniak ka ɲininiw y’a jira ko SS-31 bɛ se ka kungo kɔnɔ α-synuclein asetililen ni N-terminal acetylated α-synuclein fila bɛɛ bɔ a tata hakɛ la ka bɔ vesicles monolayer misɛnninw na minnu chargement négative bɛ u la, ka α-synuclein aggregation bali min bɛ sɔrɔ membrane fɛ, ani k’a fibrillar morphologie Changer. Ka fara o kan, SS-31 bɛ sinuklɛni jiginni segin a cogo kɔrɔ la ka bɔ jirisun misɛnninw na minnu bɛ charge négative la, ka α-sinukilini farali bali min bɛ sɔrɔ membrane fɛ, ani ka a fibrila cogoya Changer. Ka fara o kan, SS-31 bɛ se ka sinukilini jiginni segin - ka bɔ unilamellar vesicles misɛnninw na minnu chargement négative bɛ u la, ka α-SNIP aggregation induced membrane bali, ani ka a fibrillar morphology Changer. Ka fara o kan, SS-31 ye mitokondriyaw ka baara dɔgɔyali segin a cogo kɔrɔ la neuroblastoma selilɛriw la minnu furakɛra ni α-SNIP oligomɛriw ye ani ka o oligomɛri ninnu tali bali selilɛriw la. Nin sɔrɔlen ninnu bɛ SS-31 ka lakanani kɛcogo caman jira α-sinukilini farali fɛ mitokondriyaw ka baarakɛbaliya la, k’a bila jɔyɔrɔ la walasa ka farikolojidɛsɛbanaw nɔgɔya minnu bɛ tali kɛ α-sinukilini dabɔli jugu ni a dalajɛli ^la.

Dusukun ni jolisiraw ka banaw yɔrɔ

Mitokondriyaw ka baara ɲɛnabɔli dusukun tantanni banabagatɔw la: A dɔnna ko mitokondriyaw caman cili jugumanw bɛ dusukun tantanni (HF) banabagatɔw la. Kalanw ye kɔnɔbara basigilen kura furakɛ ex vivo dɛsɛlen ni dɛsɛbali la ka bɔ denmisɛnw ni balikuw la minnu bɛ ni SS-31 ye, ka oksizɛni bɔli suman mitokondriyaw la, complexe (C)I ni ​​CIV baara, ani supercomplex assembly baarakɛcogo min sinsinnen bɛ jeli kan. Chatfield ka sɔrɔw b’a jira ko mitokondriyaw ka baara dɔgɔyali hadamadenw dusukunw na minnu bɛ dɛsɛ. SS-31 furakɛli kɔfɛ, mitokondriyaw ka oksizɛni bɔli, CI ni CIV baara, ani CIV baara min bɛ tali kɛ supercomplex assembly la, olu ɲɛnabɔra kosɛbɛ, o b’a jira ko SS-31 bɛ mitokondriyaw ka baara sabati kosɛbɛ hadamaden dusukunw na minnu bɛ dɛsɛ, wa a bɛ se ka don dusukun tantanni ^na.

Barth ka bana furakɛli Dusukun tantanni : Barth ka bana ye bana ye min man ca, wa a bɛ se ka mɔgɔ faga, min bɛ tali kɛ X la, a bɛ sɔrɔ denmisɛnniw ka saya caya fɛ ani ka taa ɲɛ ka se dusukunnabana ma ni farikolo tangacogo jugumanba ye. SS-31 ye tetarapɛtidi ye min bɛ se ka ji la, katiyɔni kasadiman, min ɲɛsinnen bɛ mitokondriyaw ma, a bɛ don nɔgɔya la ani ka sigi waati dɔɔnin mitokondriyaw kɔnɔna na. A bɛ selilɛriw ka kɛnɛya sabati ani ka oksidan degun nɔgɔya a kɛtɔ ka fanga sɔrɔli bonya ani ka oksizɛni suguya caman sɔrɔli bali. Sabbah ɲininiw y’a jira ko SS-31 bɛ mitokondriyaw ka biyoɛnerji ni u cogoya ɲɛ joona joona jirisunw na minnu bɛ se ka fɛn caman kɛ, minnu bɛ bɔ Barth ka bana banabagatɔw la. Kunnafoni minnu bɔra bana caman misaliw la, olu b’a jira ko SS-31 bɛ layidu ta i n’a fɔ furakɛli min bɛ se ka kɛ Barth syndrome dusukunnabana bɛ banabagatɔ minnu na, o bɛ nɔba jira kɛrɛnkɛrɛnnenya la dusukunnabana bɛ mɔgɔ minnu na. A bɛ se ka nɔ banbali bila dusukunnabana taabolo la ka sɔrɔ a bɛ numanbolo-kɔnɔna dɛsɛlenw labɛncogo kura kɔsegin dɔɔni dɔɔni diɲɛ kɔnɔ, selilɛriw la ani molekiyɔmuw hakɛ ^la .

Farikolo ni kolotugudaw banaw yɔrɔ : Furakɛli seko jiralen don tendinopathie la. Zhang X ka sɛgɛsɛgɛli kɛra ni sosow ka supraspinatus tendinopathie modɛli ye, ka soso 126 (bolo 252) tila ka kɛ kɔrɔbɔli kulu wɔɔrɔ ye. Zhang X ka jaabiw b’a jira ko sɔgɔsɔgɔninjɛ kari fanga dɔgɔyara a sɔgɔli kɔfɛ ni i ye a suma ni sɔgɔsɔgɔninjɛ tiɲɛnenw ye. O dɔgɔyali in yɔrɔ dɔ kɔseginna klamp bɔli kɔfɛ, SS-31 furakɛli kɔfɛ, walima furakɛli faralen kɔfɛ, ni gɛlɛya bɛ o cogo kelen jira. Sɛgɛsɛgɛli min kɛra farikolo yɔrɔw la, o y’a jira ko Bonar hakɛ caman b’a la minnu sɛmɛntiyalen don, ka sɔrɔ furakɛli faralen ɲɔgɔn kan, o ye fɛn dɔw wuli ka bɔ u cogoya caman na. Jɛkulu min tɔɔrɔla, o ye mitokondriyaw hakɛ dɔgɔyali jira ani ka kirisitaw labɛncogo ni u caya caman Changé. Klanbara bɔli kɔfɛ ani/walima SS-31 furakɛli kɔfɛ, mitokondriyaw jɔcogo ni u hakɛ bɛ kɛ cogo la, ani kirisita cogoya bɛ ɲɛ. Superoxide dismutase (SOD) baara dɔgɔyara a nɔfɛko kɔfɛ ni a bɛ tali kɛ a kunbɛnbagaw la nka a cayara kosɛbɛ furakɛli kɔfɛ, kɛrɛnkɛrɛnnenya la furakɛli faralen kulu la. Mitokondriyaw ni ɲɔgɔn cɛ jamu jirali dɔgɔyara nɔ bilali kulu la nka a seginna ka segin furakɛli kɔfɛ. O b’a jira ko SS-31, n’o ye mitokondriyaw lakanani ye, o bɛ mitokondriyaw ka baara ɲɛ ani ka senkɔniw kɛnɛyali sabati, ni a nafa ka bon ni a farala ɲɔgɔn kan ni subacromial impingement removal ye. A bɛ furakɛli seko ɲuman minɛ supraspinatus tendinopathie la [8].

Kuncɛli

SS-31 (Elamipretide), i n’a fɔ tetarapɛtidi min ɲɛsinnen bɛ mitokondriyaw ma, o bɛ mitokondriyaw ka baarakɛcogo lakanani ni joginw dilancogo caman sɔrɔ. A bɛ siri fosifatidilisɛrini na mitokondriyaw kɔnɔna na, ka ɲɛgɛnɛsira jɔcogo n’a seko sabati, ka ninakili cakɛda gɛlɛnw baara caya walasa ka ATP sɔrɔli sabati, ani ka selilɛriw ka fanga sɛnɛcogo ɲɛ. O waati kelen na, a bɛ oksizɛni suguya caman (ROS) sɔrɔli bali, ka farikolo tangalanw ka baara kɛcogo kɔrɔta, ka oksidan degun tiɲɛni nɔgɔya. Ka ɲɛsin funu labɛnni ma, a bɛ NF-κB ni NLRP3 funubanakisɛw baarakɛli bali, ka dɔ bɔ funu dɛmɛbagaw bɔli la. A bɛ otofaji siraw sɛmɛntiya, ka apoptose (apoptose) bali, ka mitokondriyaw ka homeostasis (mitokondriyaw ka homeostasis) mara siraw fɛ minnu bɛ tali kɛ ɲɔgɔn na. O walew bɛ nafa caman lase banaw ma minnu bɛ kɛ ni mitokondriyaw ka baarakɛbaliya ye dusukun ni jolisiraw, hakili ni farikolo yɔrɔw bɛɛ la.

A sɛbɛnbaga ko la

Fɛn minnu kofɔlen dòn san fɛ, olu bɛɛ ɲinini Kɛra, k’u Labɛn ani k’u Lajɛ Cocer Peptides fɛ.

Dɔnniya gafe sɛbɛnbaga

Kathryn C. Chatfield ye ɲininikɛla ye Koloradugu Iniwɛrisite ka furakɛli kalanso la, min ni denmisɛnw ka kɛnɛyako ni furakɛli ɲɛmɔgɔso/dusukun furakɛli yɔrɔ dɔ bɛ ɲɔgɔn na. A bɛ a sinsin denmisɛnw ka dusukunnakow ni mitokondriyaw ka ɲɛnamayako kan, ka dusukun baara ni banaw sinsincogo fɛɛrɛw sɛgɛsɛgɛ. A ye dɛmɛba don o baara in na dɔnnikɛlaw ka sɛbɛnw ni jɛkafɔw sababu fɛ, wa a ka baara lakodɔnnen don kosɛbɛ dusukun ni jolisiraw ka farikoloɲɛnajɛ faamuyali yiriwali la ani furakɛli fɛɛrɛw minnu bɛ se ka kɛ. Kathryn C. Chatfield tɔgɔ sɛbɛnnen bɛ citation (citation) kɔnɔ [7].

▎ Sɛbɛn minnu bɛ tali kɛ o la

[1] Lafiɲɛ don HN. Elamipretide for Barth syndrome cardiomyopathy: kuran sira tiɲɛnen jɔli dɔɔni dɔɔni. Dusukun tantanni lajɛw 2022; 27(5): 1911-1923.DOI: 10.1007/s10741-021-10177-8. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[2] Mitchell W, Ng E. A., Tamucci J. D., ani a ɲɔgɔnnaw. Mitokondriyaw furakɛli SS-31 (Elamipretide) ka baarakɛcogo molekiyɔmu: Membraniw ka jɛɲɔgɔnyaw ni u nɔfɛkow surface électrostatique kan. Biorxiv 2019. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[3] Zhao W, Xu Z, Cao J, ani mɔgɔ wɛrɛw. Elamipretide (SS-31) bɛ mitokondriyaw ka baarakɛbaliya, sinankunya ni hakilijagabɔbaliya min bɛ sɔrɔ lipopolisaccharide fɛ sosow la, o ɲɛ. Journal of neuroinflammation 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[4] Zhang H, Chen Y, Li F, ani mɔgɔ wɛrɛw. Elamipretide bɛ piroptosis nɔgɔya kɔkolo joginlen na ni bɔnɛ ye, a kɛtɔ ka cPLA2-induite lysosomal membrane permeabilisation bali. Journal of neuroinflammation 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[5] Tse B. C., Dvoriantchikova G., Tao W., ani a ɲɔgɔnnaw. Furakɛli min ɲɛsinnen bɛ mitokondriyaw ma ni elamipretide (MTP-131) ye, o ye dɛmɛ ye min bɛ kɛ ka tumo necrosis factor inhibition (tumu necrosis factor inhibition) kɛ ɲɛda-la-banakisɛ jugumanba la sigida jugumanba la. Ɲɛ ɲininiw kɛra k’a lajɛ san 2020; 199: 108178.DOI:10.1016/j.exer.2020.108178. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[6] Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Peptide furakɛli SS-31 bɛ $alpha$-Synuclein ka membrane sirili ni a farali sɛmɛntiya ani ka Mitokondriyaw ka baarakɛcogo tiɲɛnen segin a cogo kɔrɔ la. Biorxiv 2024. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[7] Chatfield K. C., Sparagna G. C., Chau S., ani a ɲɔgɔnnaw. Elamipretide bɛ Mitokondriyaw ka baara ɲɛ hadamaden dusukun na min bɛ dɛsɛ. Jacc-Basic ka bamanankan baarakɛcogo dɔnniya 2019; 4(2): 147-157.DOI: 10.1016/j.jacbts.2018.12.005. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

[8] Zhang X, Bowen E, Zhang M, Szeto H. H., Deng X H., Rodeo S. A. (2006) Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew. SS-31 i n’a fɔ mitokondriyaw tangalan ye sɔgɔsɔgɔninjɛ furakɛli la: Jateminɛ kɛli sogo Supraspinatus Tendinopathie misali la. Kolow ni kolotugudaw opereli gafe-Amerika Volume 2022; 104(21): 1886-1894.DOI: 10.2106/JBJS.21.01449. Kalanjɛ ni sɛbɛnni: kalanjɛ ni sɛbɛnni gafew.

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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.