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▎ SS-31 Ọdịdị
Isi mmalite: PubChem |
Usoro: RXKF Ụdị mkpụrụ ndụ: C 32H 49N 9O5 Arọ molekụla: 639.8g/mol Nọmba CAS: 736992-21-5 PubChem CID: 11764719 Ihe atụ: Elamipretide |
▎ SS-31 Nnyocha
Kedu ihe ndabere nyocha nke SS-31?
SS-31 bụ cationic na-esi ísì ụtọ, tetrapeptide ezubere iche nke mitochondria (Sabbah HN, 2022). Ọdịdị kemịkalụ ya pụrụ iche na-enyere ya aka ịbanye n'ụzọ dị mfe ma wepụta obere oge na akpụkpọ ahụ mitochondrial dị n'ime. Kpọmkwem, ọ nwere ike jikọta na cardiolipin, bụ isi ihe dị na akpụkpọ ahụ mitochondrial dị n'ime, si otú ahụ na-arụ ọrụ ya na-eme ka ọrụ mitochondrial dịkwuo mma.
Ọdịdị kemịkal a pụrụ iche na-enye ntọala maka ntinye ya na ọgwụgwọ ọrịa dị iche iche. Ọtụtụ ọrịa na-ejikọta na mitochondrial dysfunction, dị ka ọrịa Barth, nkụda mmụọ obi, ọrịa neurodegenerative, wdg. Mgbe ọrụ mitochondrial na-adịghị mma, ọ nwere ike ibute nsogbu ndị dị ka ike cellular ezughị ezu, nrụgide oxidative na-abawanye, na neuroinflammation, nke na-ebute ọrịa dị iche iche.
Nchọpụta na mmepe nke SS-31 bu n'obi ilekwasị anya n'ọrịa ndị a metụtara mitochondrial, na-ebelata mgbaàmà ọrịa site na imeziwanye ọrụ mitochondrial na ịkwalite ogo ndụ ndị ọrịa na ọnụ ọgụgụ nlanarị. Site na nyocha miri emi na-aga n'ihu na bayoloji mitochondrial, ndị mmadụ ejirila nwayọọ nwayọọ mata mkpa mitochondria na omume na mmepe nke ọrịa.
Ndị nchọpụta achọpụtala na arụrụ ọrụ mitochondrial nwere njikọ chiri anya na usoro pathophysiological nke ọrịa dị iche iche. Dịka ọmụmaatụ, na ọrịa neurodegenerative, enwere nsogbu ndị dị ka nhụjuanya mitochondrial neuronal, neuroinflammation na-adịghị ala ala, nchịkọta protein na-egbu egbu, na apoptosis neuronal [1] . Tupu ịbanye na nyocha ụlọ ọgwụ, SS-31 mere ọtụtụ ọmụmụ ihe ọmụmụ. Ọmụmụ ihe ndị a gụnyere nnwale ndị emere na ụdị sel na ụdị anụmanụ iji nyochaa nchekwa, ịdị irè na ọgwụ ọgwụ nke ọgwụ. Dịka ọmụmaatụ, n'ime ọmụmụ banyere ọrịa Barth, SS-31 gosipụtara ikike imeziwanye bioenergetics mitochondrial na morphology ngwa ngwa n'ime ụdị mkpụrụ ndụ stem pluripotent [2]..
Na nyocha nke ọrịa neurodegenerative, SS-31 egosila mmetụta neuroprotective n'ọtụtụ ụdị anụmanụ, gụnyere ịkwalite iku ume mitochondrial, igbochi neuroinflammation, na igbochi nchịkọta protein na-egbu egbu [1] . SS-31 etinyelarị aka na ọtụtụ ọmụmụ ụlọ ọgwụ na-ekpuchi mpaghara ọrịa dị iche iche.
N'ọgwụgwọ nke nkụda obi, nyocha nke a na-achịkwaghị achịkwa, nke a na-achịkwa placebo gosipụtara na otu infusion nke SS-31 dị mma ma dị mma, na nnukwu dose SS-31 nwere ike imezi ụda ventricular aka ekpe, na-akwado ọrụ ya na ọgwụgwọ nke nkụda obi [3]..
Kedu usoro a kapịrị ọnụ nke SS-31 na ụdị ọrịa dị iche iche?
1. Usoro nke ime ihe n'ụdị nke hemorrhagic ujo na aortic balloon occlusion.
N'ihe nlereanya nke mmerụ ahụ nke ischemia-reperfusion (IRI) nke kpatara hemorrhagic shock na aortic balloon occlusion (REBOA), mmebi mitochondrial na-arụ ọrụ dị mkpa. SS-31 nwere ike belata ọchịchọ nke mmiri crystalloid ma chebe akụrụ na obi. Kpọmkwem, ọ nwere ike belata mkpokọta nke serum creatinine, troponin, na interleukin-6, mana ọ nweghị mmetụta na mkpokọta lactate plasma ikpeazụ. SS-31 nwere ike ibelata IRI site na ichekwa mitochondria, mepee ụzọ ọgwụgwọ ọhụrụ maka ndị ọrịa na-ata ahụhụ site na IRI mgbe ọbara ọgbụgba gasịrị [4].
2. Usoro ọrụ na Barth syndrome
Ọrịa Barth bụ ọrịa na-adịghị ahụkebe nke jikọrọ X nke e ji mara cardiomyopathy, adịghị ike akwara skeletal, nkwụsị uto, na neutropenia cyclic. SS-31 bụ mmiri-soluble, cationic aromatic, tetrapeptide ezubere iche nke mitochondria nke nwere ike banye n'ime mpụta mitochondrial mpụta wee jikọta na cardiolipin. Ọ na-akwalite ahụ ike cell site na ịkwalite mmepụta ume na igbochi oke nhazi nke ụdị oxygen na-emeghachi omume, si otú ahụ na-ebelata nrụgide oxidative. N'ime mkpụrụ ndụ mkpụrụ ndụ pluripotent nke Barth syndrome na ọrịa ndị ọzọ metụtara mkpụrụ ndụ ihe nketa nke e ji mara cardiomyopathy nwata, SS-31 nwere ike imeziwanye bioenergetics mitochondrial na morphology ngwa ngwa. Nsonaazụ nke ọtụtụ ọmụmụ na-akwado iji SS-31 dị ka ọgwụgwọ nwere ike maka ndị ọrịa nwere ọrịa Barth, karịsịa n'ọnọdụ ebe a chọpụtala cardiomyopathy [2].
3. Usoro nke omume na autosomal dominant polycystic akụrụ ọrịa (ADPKD)
A na-ewere ime ime ka ọ ka njọ ọganihu nke cysts na autosomal dominant polycystic akụrụ ọrịa (ADPKD). Agbanyeghị, tolvaptan, naanị ọgwụ FDA kwadoro maka okenye ADPKD, adịghị akwadoro maka ndị ọrịa ADPKD dị ime n'ihi ihe nwere ike imerụ nwa ebu n'afọ. SS-31 bụ tetrapeptide na-echebe mitochondria nke achọpụtara iji meziwanye ọganihu nke ọrịa akụrụ na ụmụ oke Pkd1RC / RC dị ime, na-ebelata ERK1/2 phosphorylation ma na-emeziwanye nhazi nke mitochondrial supercomplexes. Na mgbakwunye, SS-31 nwere ike ịgafe placenta na mmiri ara ara, na-eme ka ọrịa akụrụ polycystic na-akpa ike nke ụmụaka na-enweghị mmetụta teratogenic ma ọ bụ mmerụ ahụ. Ọmụmụ ihe ndị a na-aga n'ihu na-akwado ule ụlọ ọgwụ nwere ike nke SS-31 [5].
4. Usoro nke ime ihe na nkụda obi
Na nkụda mmụọ obi (HF), mgbanwe na-adịghị mma na mitochondria mara na ọ ga-eme. SS-31 nwere mmetụta dị mma na ọrụ mitochondrial na supercomplex nke ọdịda obi mmadụ. Ọ nwere ike ịbawanye ikuku oxygen nke ukwuu, mgbagwoju anya m na ihe omume IV dị mgbagwoju anya, yana ọrụ IV siri ike jikọtara ya na ihe mgbagwoju anya na mitochondria obi mmadụ na-esighị ike, na-eme ka ọdịda mitochondrial mmadụ dịkwuo mma ..
N'ime ụmụaka nwere ọrịa obi na-arịa otu ventricle congenital (SV CHD), ihe ngosi ụlọ ọgwụ maka ntụgharị obi na-egosi ọnụnọ nke mitochondrial dysfunction. SS-31 bụ pentapeptide ezubere iche maka cardiolipin nke nwere ike melite mmekọrịta nke mitochondrial supercomplexes (mgbagwoju anya I, III, IV). N'ime obi ụmụaka nwere SV CHD, SS-31 nwere ike imeziwanye ọrụ m mgbagwoju anya na ume iku ume (MR), na-atụ aro na ọ na-egosipụta mmetụta ya site n'ịkwalite mitochondrial supercomplexes [7].
5. Usoro nke ime ihe na ọrịa shuga nephropathy
N'ụdị òké db/db nke ụdị ọrịa shuga 2, ọrịa nephropathy na-arịa ọrịa shuga (DKD) jikọtara ya na mbelata ọkwa gbasara akụrụ na obi superoxide. Onye na-ahụ maka nchekwa mitochondria SS-31 (nke a makwaara dị ka MTP-131, SS-31, ma ọ bụ Bendavia) nwere ike igbochi mmụba nke proteinuria, urinary H₂O₂, na mkpokọta mesangial matrix glomerular na db/db ụmụ oke, ma chekwaa kpamkpam mmepụta superoxide nke akụrụngwa na ọkwa ndị a. SS-31 nwekwara ike ibelata mkpokọta renal lysocardiolipin na isi lysocardiolipin subclasses na db/db ụmụ oke, ma chekwaa okwu nke lysocardiolipin acyltransferase 1. Nsonaazụ ndị a na-egosi na n'ụdị ọrịa shuga 2, DKD jikọtara ya na mbelata nke gbasara akụrụ na obi superoxide, yana SS-31 nwere ike ichebe ọkwa nke physiguruxide site na SS-31. nhazigharị cardiolipin [8].
Eserese a na-eche echiche na-achịkọta mmetụta neuroprotective nke elamipretide na njikwa mma mitochondria neural.
Isi mmalite: PubMed [1]
Kedu ihe bụ ngwa SS-31 metụtara?
Ọrịa cardiomyopathy na ọrịa Barth: Ọrịa Barth bụ ọrịa na-adịghị ahụkebe na nke nwere ike ibute ndụ egwu nke metụtara X-njikọ nke cardiomyopathy, adịghị ike akwara skeletal, mbelata uto, na neutropenia cyclic. Ndị ọrịa nwere nnukwu ihe ize ndụ nke ịnwụ n'oge ọ bụ nwata ma na-enwekarị ike ịmalite cardiomyopathy na-esonyere oke ike ọgwụgwụ nke usoro ahụ ji alụso ọrịa ọgụ. SS-31 na-enye ma ihe ịma aka na ohere maka ọgwụgwọ cardiomyopathy na ndị ọrịa nwere ọrịa Barth. Nsonaazụ nke ọtụtụ ọmụmụ na-akwado iji ya dị ka ọgwụgwọ nwere ike maka ndị ọrịa nwere ọrịa Barth, karịsịa mgbe a chọpụtara ọrịa cardiomyopathy. Ọ nwere ike inwe mmetụta na-adịgide adịgide na ọganihu nke cardiomyopathy na nke nta nke nta na n'usoro gbanwee ngbanwe nke ventricle ekpe na-ada ada na ọkwa ụwa, cellular, na molecular [2].
Otu ventricle congenital ọrịa obi:
Ọrịa obi a mụrụ n'afọ bụ ntụpọ a na-ahụkarị n'ọmụmụ, na ọrịa obi siri ike nke otu ventricle congenital bụ isi ihe na-egosi na a na-atụgharị obi nwa ọhụrụ, yana nhọrọ ọgwụgwọ dị ole na ole dị ugbu a. Achọpụtala na enwere arụ ọrụ mitochondrial n'ime obi ụmụaka nwere ọrịa obi na-arịa otu ventricle, na peptide SS-31 ezubere iche nke mitochondria nwere ike imeziwanye ọrụ mitochondrial nke obi. Nnyocha ndị ọzọ gbasara ikike ọgwụ a iji meziwanye ọrụ myocardial na igbu oge n'ihu n'ịkwagharị dị mkpa [7].
Ihe nketa nke optic neuropathy nke Leber:
Otu ọmụmụ tụlere nchekwa, nnabata, na ịdị irè nke iji SS-31 eme ihe na ọgwụgwọ nke ndị ọrịa nwere ihe nketa optic neuropathy nke Leber. Nsonaazụ gosiri na SS-31 kwadoro nke ọma, mana o ruteghị isi njedebe arụmọrụ anya. Otú ọ dị, nyocha nke ọrụ a na-ahụ anya n'oge oge mgbatị oghere na-emeghe na nyocha nke post-hoc gosipụtara ọganihu na-agba ume na ntụgharị uche nke etiti etiti anya, nke chọrọ nyocha ọzọ [9]..
Ọrịa optic neuropathy:
Achọpụtala na SS-31 (MTP-131), obere tetrapeptide molecule nke ezubere na mitochondria, mgbe ejiri ya na tumor necrosis factor inhibitor etanercept, nwere ike ije ozi dị ka neuroprotectant maka mkpụrụ ndụ ganglion retina mgbe ọnya akwara optic na ụmụ oke. Subcutaneous etanercept ma ọ bụ MTP-131 naanị na nchikota ha niile nwere ike ime ka ọnụọgụ ndụ nke mkpụrụ ndụ retinal ganglion dịkwuo elu, mana ọ nweghị mmetụta synergistic a hụrụ mgbe ejiri ya na ngwakọta [10]..
Ọkpụkpụ azụ mmerụ ahụ: SS-31 (SS-31) bụ akwụkwọ akụkọ aromatic cationic peptide nke nwere ike ịgafe ihe mgbochi ụbụrụ ọbara n'efu. Nnyocha egosiwo na SS-31 na-akwalite mgbake na-arụ ọrụ mgbe mmerụ ahụ ọkpụkpụ azụ gasịrị site na igbochi cPLA2-mediated autophagic mmebi, na-egbochi mmụba nke lysosomal membrane permeability, na igbochi pyroptosis, na ọ nwere ikike ngwa ngwa ngwa [11].
Neuroinflammation na nhụsianya uche:
Na oke oke, lipopolysaccharide nwere ike ibute mbufụt sistemu na neuroinflammation, yana SS-31 nwere ike iji maka ọgwụgwọ. Nnyocha e mere egosiwo na igbochi hippocampal neuroinflammation nwere ike ọ bụghị nanị ibelata nzaghachi mkpali na hippocampus kamakwa melite njikọ ọrụ nke ụbụrụ na mpaghara ndị metụtara hippocampus. Ọgwụgwọ mgbochi mkpali n'oge na SS-31 nwere mmetụta na-adịgide adịgide na mbenata mmetụta nke lipopolysaccharide na-ebute neuroinflammation [12].
Ọrịa akụrụ polycystic na-akpata autosomal:
A na-ewere ime ime ka ọ ka njọ ọganihu nke cysts na autosomal na-achị ọrịa akụrụ polycystic. Achọpụtara na mitochondria-protective tetrapeptide SS-31 nwere ike imeziwanye ọganihu nke ọrịa akụrụ n'ime ụmụ oke Pkd1 ^ {RC/RC} dị ime, na-ebelata ERK1/2 phosphorylation na imeziwanye nhazi nke mitochondrial supercomplexes. SS-31 nwere ike ịgafe placenta na mmiri ara ara, na-eme ka ọrịa akụrụ polycystic siri ike nke ụmụaka na-enweghị mmetụta teratogenic ma ọ bụ mmetụta ọjọọ [5].
Ọrịa neurodegenerative:
SS-31 bụ obere tetrapeptide molecule ezubere iche nke mitochondria nke gosipụtara mmetụta ọgwụgwọ na nchekwa na ọrịa dị iche iche metụtara mitochondrial. Na ọrịa neurodegenerative, SS-31 nwere ike welie mitochondrial respiration, rụọ ọrụ neuronal mitochondrial biogenesis site mitochondrial biogenesis regulators na translocator ihe, welie mitochondrial fusion, na-egbochi mitochondrial fission, na-amụba mitophagy, belata neuronal oxidative stress, neuroinflammation, na protin apoptosis neuronal na-egbochi neuronal survivosis, neuronflammation. ụzọ. Ya mere, SS-31 nwere ike igbochi ọganihu nke ọrịa neurodegenerative site n'ịkwalite respiration mitochondrial, biogenesis, fusion, na neuronal ụzọ ndụ ndụ, yana igbochi mitochondrial fission, nrụgide oxidative, neuroinflammation, nchịkọta protein na-egbu egbu, na apoptosis neuronal [1]..
Sarcopenia: Achọpụtara na izu 8 nke ọgwụgwọ na SS-31 nwere ike gbanwee mgbanwe ndị metụtara afọ na protein phosphorylation na skeletal muscle nke ụmụ oke nwanyị merela agadi, bụ nke kwekọrọ na mmelite nke ọrụ ọkpụkpụ skeletal na mweghachi nke mgbanwe na protein S-glutathionylation [13].
Dị ka ọgwụ ezubere iche maka mitochondria, SS-31 na-enye atụmatụ ọhụrụ maka ọgwụgwọ ọrịa mitochondrial. Site n'ichekwa ihe owuwu na ọrụ nke mitochondria, o gosipụtala uru ụlọ ọgwụ na ọrịa ndị dị ka LHON na ọrịa Barth, karịsịa na-egosi nrụpụta dị ịrịba ama na nnukwu neuropathy optic. Ọ nwere mmetụta ọgwụgwọ na ọrịa dị iche iche metụtara mitochondrial dysfunction, dị ka nkụchi obi na ọrịa neurodegenerative, ma nwee ike ịkwụsị mgbaàmà ma gbuo oge ọganihu nke ọrịa ahụ.
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
Daneshgar N bụ ọkà mmụta nwere mmetụta na mpaghara agụmakwụkwọ, yana ọrụ agụmakwụkwọ ya jikọtara ya na Mahadum Iowa na Mahadum Oregon State. Mpaghara nyocha ya dị ukwuu ma dị omimi, na-ekpuchi ọtụtụ ọzụzụ dị ka geriatrics na gerontology, sistemu obi na akwara obi, biochemistry na biology molecular, biology cell, na oncology. N'ihe gbasara geriatrics na gerontology, Daneshgar N na-agba mbọ ịchọpụta usoro ndu nke ịka nká na ntinye aka dị irè maka ọrịa ndị metụtara ịka nká, na-atụ anya imeziwanye ndụ ndụ na ahụike nke ndị agadi site na nyocha.
N'akụkụ nke usoro obi na akwara obi, ọ na-eme nchọpụta miri emi banyere pathogenesis, ụzọ nchọpụta, na usoro ọgwụgwọ nke ọrịa obi, na-enye aka na mgbochi na ọgwụgwọ nke ọrịa obi. N'ihe gbasara biochemistry na ihe ndị dị ndụ, ọ na-elekwasị anya na nhazi, ọrụ, na mmekọrịta nke biomolecules, na-ekpughe ihe omimi nke ihe omume ndụ na ọkwa molecular na inye ihe ndabere maka nghọta na ọgwụgwọ ọrịa. N'ihe gbasara usoro ihe ọmụmụ cell, Daneshgar N na-elekwasị anya na nhazi, ọrụ, na iwu nke ọrụ ndụ nke mkpụrụ ndụ, na-amụ usoro ndị dị mkpa dị ka nsụgharị cell cell transduction na cell cell cell, na-enye ihe ngosi dị mkpa maka nyocha nke usoro cellular nke ọrịa. N'ihe gbasara oncology, ọ na-etinye aka na nyocha banyere ihe omume na usoro mmepe nke etuto ahụ, yana nchọpụta na ọgwụgwọ nke etuto ahụ, na-enyocha akara nrịbama n'oge na ebumnuche ọgwụgwọ ọhụrụ maka etuto ahụ, na-eweta olileanya ọhụrụ nye ndị ọrịa tumor. Edepụtara Daneshgar N na ntụnye aka [5].
