SS31 50mg

▎ SS-31 Ọdịdị

▎ SS-31 Nnyocha

Kedu ihe ndabere nyocha nke SS-31?

Nchọpụta nyocha nke SS-31 sitere na nghọta miri emi nke dysfunction mitochondrial na njedebe nke ụzọ ọgwụgwọ dị adị. Mitochondria bụ ihe dị mkpa maka ọrụ na ọrụ cellular, na arụ ọrụ ha na-ejikọta na mmalite na ọganihu nke ọrịa dị iche iche, dị ka ọrịa akụrụ, ọrịa neurodegenerative, na nkụda obi. N'ọnọdụ ndị a, ihe na-adịghị mma na mitochondrial biogenesis, morphology, ọrụ, na mgbanwe dị egwu na-apụta, na-eme ka mitochondria bụrụ ebumnuche ọgwụgwọ dị egwu. Ọ bụ ezie na ọtụtụ ọgwụ ezubere iche maka mitochondrial dị-gụnyere NAD + ihe mgbakwunye dị ka nicotinamide mononucleotide (NMN), MitoQ na-echekwa mitochondrial-ezubere iche, yana antioxidant coenzyme Q10—ọgwụ ọdịnala na-eche oke ụlọ ọgwụ ihu n'ihi nnabata mitochondrial dara ogbenye ma ọ bụ oke nsi. N'ihi ya, ọ dị mkpa ka ọ zụlite usoro ọgwụgwọ dị irè karị, nke ezubere iche.

Obi mgbawa na-akpata nrụgide na-anọchite anya otu n'ime isi ihe na-akpata nkụda obi n'ụwa nile, yana pathophysiology ya jikọtara ya na nkwụsị nke mitochondrial na myocardial interstitial fibrosis. Ịmata usoro ọgwụgwọ dị irè dị oke mkpa maka imeziwanye nsonaazụ onye ọrịa. N'imegide ndabere a, ndị nchọpụta mepụtara SS-31, ihe ọhụrụ antioxidant mitochondrial-ezubere iche, iji gboo mkpa ọgwụgwọ maka ọrịa ndị metụtara mitochondrial dysfunction. Ọ na-arụ ọrụ kpọmkwem na akpụkpọ anụ mitochondrial dị n'ime, na-eme ka nhazi na ọrụ mitochondrial guzosie ike ma na-ebelata nrụgide oxidative, na-egosipụta ịdị irè n'ọtụtụ ụdị ọrịa.

Gịnị bụ usoro nke edinam nke SS-31?

Na-achịkwa ọrụ akpụkpọ ahụ mitochondrial

Mmekọrịta ya na cardiolipin: Elamipretide na-agafe akpụkpọ ahụ mitochondrial nke mpụta wee jikọta na cardiolipin. Cardiolipin bụ isi akụkụ phospholipid nke n'ime mitochondrial membrane, na-arụ ọrụ dị mkpa n'ịkwado nhazi na ọrụ mitochondrial. Site na mmekorita a, Elamipretide na-emeziwanye bioenergetics mitochondrial na morphology. Usoro a na-egosipụta dị ka mmụba ngwa ngwa nke ọrụ mitochondrial n'ime mkpụrụ ndụ sel pluripotent na-ebute, karịsịa na sel ndị sitere na ndị ọrịa nwere ọrịa Barth na ọrịa cardiomyopathies ụmụaka ndị ọzọ ketara eketa ^[1].

Na-agbanwe Njirimara anụ ahụ nke akpụkpọ ahụ: Nchọpụta Mitchell W na-egosi na Elamipretide na-emekọrịta ihe na bilayer lipid, na-agbanwe njirimara anụ ahụ nke akpụkpọ ahụ mitochondrial, karịsịa ihe ndị dị na electrostatic na interface membrane. Nke a peptide na-ekesa na mpaghara ihu igwe akpụkpọ ahụ yana njupụta na njupụta jikọtara ya na ụgwọ elu. Ọ bụ ezie na ọ naghị eme ka ọkpụkpụ lamellar ghara ịdị n'otu n'ogo dị elu, ọ na-ebute mgbanwe saturation na nchịkọta lipid, si otú ahụ na-emetụta ọrụ akpụkpọ anụ mitochondrial ^[2]..

Ọgụgụ 1 Ihe na-emetụta ọkọnọ ike na ọchịchọ obi ^[1].

Ichekwa sistemu akwara ozi

Ịkwalite ọrụ ọgụgụ isi: N'ime ụdị òké lipopolysaccharide (LPS) kpatara nsogbu ebe nchekwa, ọgwụgwọ Elamipretide mere ka mmụta dịkwuo mma na ikike ncheta na Morris water maze (MWM) na ọnọdụ ọnọdụ ụjọ. Enwere ike jikọta mmetụta a na-eme ka ahụ dịkwuo mma na nchebe ya nke ọrụ mitochondrial, mbelata nrụgide oxidative, nhazi nke ụbụrụ neurotrophic factor (BDNF) na-egosi ụzọ mgbaàmà, na nkwalite nke mgbagwoju anya nhazi synaptic. Ọgwụgwọ LPS kpalitere dysfunction mitochondrial, nchekasị oxidative, mbufụt, neuronal apoptosis, na dendritic spine ọnwụ na òké hippocampus, ebe Elamipretide belatara mmerụ ndị a, na-egosipụta ike na igbochi perioperative neurocognitive dysfunction (PND) ^[3].

Mgbochi nke Neuronal Apoptosis: N'ihe ọmụmụ ihe gbasara ọkpụkpụ azụ (SCI), Elamipretide na-akwalite mgbake ọrụ site n'ịkwụsị pyroptosis, na-eme ka autophagy dịkwuo elu, na ibelata lysosomal membrane permeability (LMP). Ọ na-akwalite autophagy site na igbochi cPLA2 phosphorylation mgbe ọ na-ebelata pyroptosis na LMP. Ya mere, Elamipretide na-arụ ọrụ dị mkpa n'imezi mmerụ ahụ akwara site na ịhazi ọtụtụ usoro cellular, ibelata apoptosis neuronal, na ịkwalite mgbake ọrụ akwara ^[4]..

Ọgụgụ 2 Elamipretide (SS-31) na-ebelata nrụgide oxidative na nzaghachi mkpali nke LPS kpatara na hippocampus òké. ụdị oxygen na-emeghachi omume (ROS), ọkwa b malondialdehyde (MDA), yana ọrụ c superoxide dismutase (SOD) ^[3].

Kedu ihe bụ ngwa SS-31?

Ọrịa Neurological

Ọgwụgwọ nke Neuropathy Optic Neuropathy: Traumatic optic neuropathy (TON) nwere ike ime ka ọhụụ ọhụụ na-adịgide adịgide n'ihi trauma orbital na-adịghị mma. Nnyocha enyochala mmetụta neuroprotective nke SS-31 jikọtara ya na ụbụrụ necrosis factor (TNF) inhibitor etanercept na retinal ganglion cell (RGCs) na-eso mmerụ ahụ akwara optic. Nnyocha nke Tse BC site na iji ụdị TON nke na-akpata ultrasound (SI-TON) chọpụtara na ntụtụ intravitreal nke SS-31 jikọtara ya na injection subcutaneous nke etanercept na SS-31 mụbara ndụ RGC site na 21% (p <0.01) ma e jiri ya tụnyere phosphate-buffered saline (PBS) -emeso anya nchịkwa. Ngwakọta nke etanercept subcutaneous na SS-31 mụbara nlanarị RGC site na 11% (p <0.05) ma e jiri ya tụnyere njikwa; Ọkpụkpụ subcutaneous nke etanercept naanị mụbara nlanarị RGC site na 20% (p <0.01) ma e jiri ya tụnyere njikwa; Ngwunye subcutaneous nke SS-31 naanị mụbara nlanarị RGC site na 17% ma e jiri ya tụnyere otu njikwa (p <0.01). Nchọpụta ndị a na-egosi na SS-31 na-arụ ọrụ nchebe na RGCs n'ịgwọ ọrịa neuropathy na-ahụ anya, si otú ahụ na-eme ka anya na-ahụ anya na ndị ọrịa TON ^[5].

Mmelite na α-Synuclein-Mekọrịtara Neurodegenerative Ọrịa: Ọrịa Parkinson na synucleinopathies metụtara na-ejikọta ya na akpụkpọ ahụ na-ejikọta na nchịkọta nchịkọta nke α-synuclein. Nnyocha Stefaniak na-akwado na SS-31 nwere ike ịdabere na ya na-ewepụ ma ụdị anụ ọhịa na N-terminal acetylated α-synuclein site na ebubo obere monolayer vesicles na-adịghị mma, na-egbochi nchịkọta α-synuclein na-akpata akpụkpọ ahụ, ma gbanwee morphology fibrillar ya. Ọzọkwa, SS-31 na-eweghachi nchụpụ nke synuclein site na obere vesicles monolayer ebubo na-ezighị ezi, na-egbochi nchịkọta α-synuclein na-eme ka akpụkpọ ahụ pụta, ma gbanwee ọdịdị ọdịdị fibrillar ya. Tụkwasị na nke ahụ, SS-31 nwere ike iweghachi nchụpụ nke synuclein - site na obere vesicles unilamellar ebubo na-ezighị ezi, na-egbochi nchịkọta α-SNIP nke akpụkpọ ahụ na-ebute, ma gbanwee ọdịdị ọdịdị fibrillar ya. Ọzọkwa, SS-31 weghachiri ọrụ mitochondrial na-adịghị mma na sel neuroblastoma nke ejiri α-SNIP oligomers mesoo ma gbochie nnabata cellular nke ndị oligomer a. Nchọpụta ndị a na-egosipụta mmetụta nchebe dị iche iche nke SS-31 megide α-synuclein aggregation-induced mitochondrial dysfunction, na-etinye ya iji belata ọrịa neurodegenerative metụtara α-synuclein misfolding na aggregation ^[6]..

Ngalaba Ọrịa obi obi

Ịkwalite ọrụ Mitochondrial na ndị ọrịa na-ada mbà n'obi: Mgbanwe mitochondrial ọjọọ mara na ọ dị na ndị ọrịa obi obi (HF). Nnyocha na-emeso anụ ahụ ventricular ọhụrụ ex vivo na-adịghị ada ada site na ụmụaka na ndị okenye nwere SS-31, na-atụle ikuku oxygen mitochondrial, mgbagwoju anya (C) I na CIV, na ọrụ dabeere na gel nke mgbakọ ukwu. Nchọpụta Chatfield na-egosi adịghị arụ ọrụ mitochondrial na-adaba n'obi mmadụ. N'ịgbaso ọgwụgwọ SS-31, ikuku oxygen mitochondrial, ọrụ CI na CIV, na ọrụ CIV metụtara mgbakọ supercomplex mere ka ọ dịkwuo mma, na-egosi SS-31 na-eme ka ọrụ mitochondrial na-adaba obi mmadụ ma nwee ike itinye aka na nkụda mmụọ ^[7]..

Ọgwụgwọ nke Barth Syndrome Cardiomyopathy: Ọrịa Barth bụ ọrịa na-adịghị ahụkebe na nke nwere ike igbu X-njikọ nke e ji mara oke ụmụ ọhụrụ na-anwụ anwụ na ọganihu na cardiomyopathy nwere nnukwu usoro ahụ ji alụso ọrịa ọgụ. SS-31 bụ cationic na-esi ísì ụtọ, tetrapeptide ezubere iche nke mitochondrial nke na-abanye ngwa ngwa ma na-agbadata na akpụkpọ ahụ mitochondrial dị n'ime. Ọ na-akwalite ahụ ike cell ma na-ebelata nrụgide oxidative site n'ịkwalite mmepụta ume na igbochi oke ikuku oxygen na-emeghachi omume. Nnyocha Sabbah gosipụtara na SS-31 na-eme ngwa ngwa na-emeziwanye bioenergetics mitochondrial na morphology n'ime mkpụrụ ndụ sel pluripotent ewepụtara site na ndị ọrịa nwere ọrịa Barth. Data sitere na ụdị ọrịa dị iche iche na-egosi SS-31 na-ekwe nkwa dị ka ọgwụgwọ nwere ike maka ndị ọrịa nwere ọrịa obi na-arịa ọrịa Barth, na-egosipụta mmetụta pụtara ìhè na ndị a chọpụtara na ha nwere cardiomyopathy. Ọ nwere ike ịkpata mmetụta na-adịgide adịgide na ọganihu cardiomyopathy ka ọ na-eji nwayọọ nwayọọ na-agbanwegharị nhazi nke ventricles aka ekpe na-ada ada na ọkwa ụwa, cellular, na molecular ^[1] .

Ngalaba Ọrịa Musculoskeletal: E gosipụtara ike ọgwụgwọ na tendinopathy. Ọmụmụ Zhang X jiri ihe nlere anya supraspinatus tendinopathy òké na-ekewa ụmụ oke 126 (ụkwụ 252) n'ime otu nnwale isii. Nsonaazụ sitere na Zhang X na-egosi na ike mgbawa akaị na-ebelata mmetụta mgbe e jiri ya tụnyere akwara ndị na-emebibeghị. Mbelata a tụgharịrị n'otu akụkụ ka ewepụrụ mwepu, ọgwụgwọ SS-31, ma ọ bụ ọgwụgwọ jikọtara ọnụ, yana isi ike gosipụtara ụkpụrụ yiri ya. Nyocha akụkọ ihe mere eme gosipụtara akara Bonar gbanwetụrụ dị elu na otu mmetụta, ebe ọgwụgwọ jikọtara ya na akụkụ ụfọdụ tụgharịrị mgbanwe morphological na akwara. Ndị otu ahụ emetụtara gosipụtara ọnụọgụ mitochondrial belatara ma gbanwee nhazi cristae na njupụta. Na-eso mwepu na/ma ọ bụ ọgwụgwọ SS-31, nhazi nke mitochondrial na ọnụọgụ ya ahazigharịrị, na morphology cristae na-akawanye mma. Ọrụ Superoxide dismutase (SOD) belatara mmetụta mgbe e jiri ya tụnyere njikwa mana ọ na-abawanye nke ukwuu mgbe ọgwụgwọ gasịrị, ọkachasị na otu ọgwụgwọ jikọtara ọnụ. Okwu mkpụrụ ndụ metụtara Mitochondria gbadara n'ime otu mmetụta mana ọ maliteghachiri mgbe ọgwụgwọ gasịrị. Nke a na-egosi na SS-31, dị ka onye na-echebe mitochondrial, na-eme ka ọrụ mitochondrial dịkwuo mma ma na-akwalite ọgwụgwọ akwara, na-arụ ọrụ nke ọma mgbe ejikọtara ya na nkwụsị nke subcromial impingement. Ọ na-ejide ikike ọgwụgwọ dị mma maka supraspinatus tendinopathy [8].

Mmechi

SS-31 (Elamipretide), dị ka tetrapeptide ezubere iche nke mitochondrial, na-enweta nchebe ọrụ mitochondrial na nrụzi mmerụ ọtụtụ sistemụ. Ọ na-ejikọta na phosphatidylserine na akpụkpọ anụ mitochondrial dị n'ime, na-eme ka usoro akpụkpọ ahụ dị ike na ikike ya, na-eme ka ọrụ mgbagwoju anya nke iku ume iji kwalite mmepụta ATP, na imeziwanye ike nke cellular. N'otu oge ahụ, ọ na-egbochi ọgbọ ụdị oxygen na-arụ ọrụ nke ukwuu (ROS), na-akwalite ọrụ enzyme antioxidant, ma na-ebelata mmebi nrụgide oxidative. N'ihe gbasara ụkpụrụ mkpali, ọ na-egbochi NF-κB na NLRP3 mkpali na-egbuke egbuke, na-ebelata ntọhapụ pro-inflammatory. Ọ na-agbanwe ụzọ autophagy, na-egbochi apoptosis, ma na-ejigide homeostasis mitochondrial site na ụzọ ndị metụtara ya. Omume ndị a na-enye mmetụta bara uru na ọrịa ndị metụtara arụ ọrụ mitochondrial n'ofe obi, akwara ozi, na sistem musculoskeletal.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Kathryn C. Chatfield bụ onye nyocha na Mahadum nke Colorado School of Medicine, jikọtara ya na Ngalaba Pediatrics na Medicine / Nkeji Cardiology. Ọ na-elekwasị anya na ọrịa obi ụmụaka na mitochondrial biology, na-enyocha usoro ndị na-akpata ọrụ obi na ọrịa. O tinyela aka na mpaghara ahụ site na akwụkwọ ndị ọkà mmụta na mmekorita, a na-amakwa ọrụ ya maka ịkwalite nghọta nke physiology nke obi na usoro ọgwụgwọ nwere ike. Kathryn C. Chatfield ka edepụtara na ntụnye aka [7].

▎ Okwu ndị dị mkpa

[1] Sabbah HN. Elamipretide maka Barth syndrome cardiomyopathy: wughachi nwayọ nwayọ nke grid ike dara ada. Nyochaa ọdịda obi 2022; 27 (5): 1911-1923.DOI: 10.1007/s10741-021-10177-8.

[2] Mitchell W, Ng EA, Tamucci JD, et al. Usoro Molecular nke Omume nke Mitochondrial Therapeutic SS-31 (Elamipretide): Mmekọrịta Membrane na Mmetụta na Elu Electrostatics. Biorxiv 2019. https://api.semanticscholar.org/CorpusID:202016574.

[3] Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) na-eme ka arụrụ ọrụ mitochondrial, nsogbu synapti na ebe nchekwa na-ebute site na lipopolysaccharide na ụmụ oke. Akwụkwọ akụkọ Neuroinflammation 2019; 16(1): 230.DOI: 10.1186/s12974-019-1627-9.

[4] Zhang H, Chen Y, Li F, et al. Elamipretide na-ebelata pyroptosis n'ọkpụkpụ azụ nke merụrụ ahụ site na igbochi cPLA2 na-ebute lysosomal membrane permeabilization. Akwụkwọ akụkọ Neuroinflammation 2023; 20(1): 6.DOI: 10.1186/s12974-023-02690-4.

[5] Tse BC, Dvoriantchikova G, Tao W, et al. Usoro ọgwụgwọ ezubere iche nke Mitochondrial na elamipretide (MTP-131) dị ka ihe mgbakwunye na mgbochi necrosis nke tumor maka akwara optic neuropathy na nnukwu ọnọdụ. Nnyocha anya nnwale 2020; 199: 108178.DOI:10.1016/j.exer.2020.108178.

[6] Stefaniak E, Cui B, Sun K, Yan X, Teng X, Ying L. Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of $alpha$-Synuclein and Weghachite Mmera Mitochondrial Ọrụ. Biorxiv 2024. https://api.semanticscholar.org/CorpusID:271162443.

[7] Chatfield KC, Sparagna GC, Chau S, et al. Elamipretide na-eme ka ọrụ Mitochondrial dị na obi mmadụ na-ada ada. Jacc-Basic ruo Sayensị Ntụgharị Asụsụ 2019; 4(2): 147-157.DOI: 10.1016/j.jacbts.2018.12.005.

[8] Zhang X, Bowen E, Zhang M, Szeto HH, Deng XH, Rodeo SA. SS-31 dị ka onye na-echebe Mitochondrial na ọgwụgwọ nke Tendinopathy: Nyocha na Murine Supraspinatus Tendinopathy Model. Akwụkwọ akụkọ nke ọkpụkpụ na ịwa ahụ nkwonkwo-Mpịakọta America 2022; 104 (21): 1886-1894.DOI: 10.2106/JBJS.21.01449.

Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadobeghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.