SS-31 (Elamipretide): Ib qho tshwj xeeb Mitochondria-Targeting Peptide rau Cellular Protection thiab noj qab nyob zoo

Nyob rau hauv xyoo tas los no, kev loj hlob sai tau raug coj mus rau mitochondria- cov hom phiaj sib txuas xws liSS-31 (Elamipretide). Qhov no hluavtaws peptide xaiv khaws cia nyob rau hauv lub puab mitochondrial membrane, qhov twg nws khi rau cardiolipin, ib tug phospholipid tseem ceeb rau kev tswj mitochondrial kev ncaj ncees thiab muaj nuj nqi. Los ntawm kev kho cov mitochondrial kev noj qab haus huv, SS-31 tau pom tias muaj peev xwm tseem ceeb rau kev txo qis kev ua haujlwm mitochondrial thiab muab kev cia siab rau kev kho mob rau cov mob xws li pob txha pob txha atrophy, Alzheimer's kab mob, kab mob plawv, thiab hnub nyoog ntawm cellular poob.

Nws txoj kev kho mob muaj peev xwm nthuav dav ntau thaj chaw, los ntawm kev txo qis cov pa oxygen reactive (ROS) thiab txhim kho cellular bioenergetics los txhawb kev noj qab haus huv thiab kev noj qab haus huv. Raws li kev tshawb fawb nce ntxiv, SS-31 tau tshwm sim los ua tus neeg sib tw muaj txiaj ntsig rau kev tiv thaiv kab mob degenerative thaum txuas ntxiv kev noj qab haus huv.

TSI-31, kuj hu uaElamipretide, yog mitochondria - tsom rau cov khoom siv hluavtaws tetrapeptide uas xaiv khi raucardiolipin, phospholipid nyob rau hauv lub puab mitochondrial membrane. Cardiolipin ua lub luag haujlwm tseem ceeb hauv kev tswj hwm mitochondrial membrane kev ncaj ncees thiab ua kom yooj yim rau kev thauj mus los hauv hluav taws xob hauv hluav taws xob xa hluav taws xob (ETC) (Szeto, 2006).

Los ntawm stabilizing cardiolipin, SS-31 pab khaws cia mitochondrial membrane muaj peev xwm, txo qis kev tsim cov pa oxygen reactive (ROS), thiab tswj ATP synthesis. Cov kev sib xyaw ua ke no pab tiv thaiv mitochondrial dysfunction cuam tshuam nrog kev laus thiab ntau yam kab mob degenerative (Manczak li al., 2010; Shi li al., 2019).

Vim tias cov khoom tshwj xeeb no, SS-31 tau dhau los ua tus neeg sib tw kho mob zoo rau cov xwm txheej suav nrog Alzheimer's kab mob, cov leeg pob txha atrophy, thiab kab mob plawv (Campbell li al., 2021; Lub taub hau li al., 2019).

Mitochondria feem ntau tau piav qhia tias yog "powerhouses" ntawm lub xov tooj ntawm tes, tab sis lawv txoj haujlwm txuas mus deb dhau ntawm ATP ntau lawm. Lawv yog qhov tseem ceeb rau kev tswj hwm calcium, apoptosis, thiab ROS homeostasis. Thaum mitochondrial kev ua haujlwm poob qis, nws ua rau muaj kev cuam tshuam ntau yam, nrog rau cov kab mob neurodegenerative, nqaij ntshiv, hlab plawv, thiab ua rau kev laus sai. Los ntawm kev tiv thaiv cardiolipin thiab stabilizing lub puab mitochondrial daim nyias nyias, SS-31 sawv cev rau ib tug tseem ceeb breakthrough nyob rau hauv mitochondrial tshuaj.

Cov qauv molecular tshwj xeeb ntawm SS-31 ua rau nws nkag mus ncaj qha rau hauv mitochondrial daim nyias nyias. Ib zaug hauv mitochondria, nws xaiv khi rau cardiolipin, ib qho lipid tshwj xeeb rau mitochondrial membrane uas tswj cov txheej txheem membrane thiab optimizes electron thauj saw muaj nuj nqi.

Kev poob ntawm cardiolipin kev ncaj ncees impairs ATP ntau lawm thaum nce ROS tiam, thaum kawg pab rau cellular aging thiab kab mob kev loj hlob (Szeto, 2006).

Los ntawm kev khaws cia cov qauv cardiolipin, SS-31 txo cov electron to thiab suppresses ntau dhau ROS tsim. Tsis zoo li cov tshuaj tiv thaiv kab mob antioxidants uas tshem tawm cov dawb radicals tom qab lawv tsim, SS-31 ua dej ntws los ntawm kev ruaj khov mitochondrial nws tus kheej. Qhov no mitochondria-targeted mechanism tso cai rau nws khaws cia mitochondrial kev ua haujlwm ntawm nws qhov chaw, muab cov txiaj ntsig kho mob dav dav (Manczak li al., 2010).

ROS ntau dhau ua rau cov protein, lipids, thiab DNA, ua rau cov kab mob sib kis thiab cov kab mob degenerative. Thaum laus, oxidative kev nyuaj siab feem ntau overwhelms lub cev endogenous antioxidant tiv thaiv systems.

SS-31 hais txog qhov teeb meem no los ntawm kev txhim kho mitochondrial efficiency thiab txo ROS ntau lawm ntawm nws qhov chaw. Tsis yog tsuas yog neutralizing dawb radicals, nws txo lawv cov tsim los ntawm kev txhim kho mitochondrial muaj nuj nqi.

Cov kev tshawb fawb tau pom tias SS-31 txo qis cov cim kev ntxhov siab oxidative hauv cov leeg pob txha thiab cov paj hlwb. Cov kev txo qis no tau nrog cov qib qis ntawm cov kab mob biomarkers, qhia tias peptide muaj txiaj ntsig zoo tsis yog tsuas yog kev ua haujlwm mitochondrial xwb tab sis kuj muaj qhov dav ntawm cellular (Zhou li al., 2019).

4.1 Skeletal Muscle Atrophy

Mitochondrial dysfunction yog ib qho tseem ceeb rau sarcopenia thiab hnub nyoog - cuam tshuam cov leeg nqaij. SS-31 pab tiv thaiv cov teebmeem no los ntawm kev txhim kho mitochondrial ATP ntau lawm thaum txo oxidative puas los ntawm ROS.

Cov kev tshawb fawb tsiaj tau pom tias muaj kev txhim kho hauv cov leeg nqaij, lub zog, thiab kev ua haujlwm tom qab SS-31 kev kho mob, qhia tias nws muaj peev xwm ncua lossis tiv thaiv hnub nyoog txog cov leeg pob txha. Cov kev tshawb pom no qhia tias SS-31 tuaj yeem pab cov neeg laus muaj kev txav mus los, kev ywj pheej, thiab lub neej zoo (Campbell li al., 2021).

4.2 Cov Kab Mob Neurodegenerative thiab Alzheimer's Disease

Alzheimer's disease (AD) yog tus cwj pwm los ntawm mitochondrial abnormalities thiab oxidative kev nyuaj siab.

Hauv kev sim AD qauv, SS-31 tau qhia txhawb nqa cov txiaj ntsig los ntawm kev txo qis ROS qib, rov ua haujlwm mitochondrial, thiab ua kom cov kab mob qeeb. Txhim kho mitochondrial stability tuaj yeem pab tswj kev noj qab haus huv neuronal thiab tswj kev txawj ntse rau lub sijhawm ntev (Lub taub hau li al., 2019).

4.3 Kab mob plawv

Lub plawv muaj ib qho ntawm qhov siab tshaj plaws ntawm mitochondria hauv lub cev, thiab mitochondrial ua haujlwm tsis zoo yog cuam tshuam nrog lub plawv tsis ua haujlwm.

Los ntawm kev tiv thaiv cardiolipin thiab txhim kho mitochondrial kev ua tau zoo, SS-31 tau pom tias yuav txo tau cov mob plawv thiab txhim kho lub plawv ua haujlwm hauv cov kev tshawb fawb preclinical. Cov kev tshawb pom no qhia tias SS-31 tuaj yeem pab ua kom lub plawv tsis ua haujlwm qeeb thaum txhim kho lub neej zoo rau cov neeg mob uas muaj kab mob plawv (Shi li al., 2019).

Txawm hais tias SS-31 (Elamipretide) tau pom tias muaj peev xwm kho tau zoo rau mitochondrial tsis ua haujlwm, qee qhov teebmeem tshwm sim tau raug tshaj tawm thaum lub sijhawm kho mob.

Cov xwm txheej tsis zoo uas tshwm sim feem ntau yog mob me mus rau nruab nrab thiab suav nrog kev txhaj tshuaj - qhov tshwm sim ntawm qhov chaw, xeev siab, mob taub hau, thiab qaug zog. Cov kev mob tshwm sim no feem ntau yog ncua sij hawm thiab tswj tau (Szeto, 2006; Manczak li al., 2010).

Vim tias SS -31 ncaj qha hloov kho mitochondrial muaj nuj nqi, kuj tseem muaj qhov kev pheej hmoo ntawm kev cuam tshuam ntawm cellular zog homeostasis thaum lub sij hawm kev tswj hwm mus sij hawm ntev, tshwj xeeb tshaj yog nyob rau hauv nruab nrog cev nrog siab mitochondrial turnover xws li lub plawv thiab skeletal leeg (Campbell li al., 2021).

Kev tshawb fawb soj ntsuam ntxiv yog tsim nyog los soj ntsuam tag nrho lub sij hawm ntev - kev nyab xeeb profile ntawm SS-31 nyob rau hauv ntau tus neeg mob thiab cov kab mob (Shi li al., 2019).

SS-31 tau nyiam ntau yam hauv lub zej zog lub neej ntev tsis yog rau nws qhov kev hloov kho kab mob nkaus xwb tab sis kuj rau nws lub peev xwm los tawm tsam cellular aging ntawm nws qhov chaw.

Txij li thaum mitochondrial tsis ua haujlwm tau lees paub tias yog ib qho ntawm cov cim tseem ceeb ntawm kev laus, kev txhim kho mitochondrial kev noj qab haus huv tuaj yeem pab txhawb kev noj qab haus huv.

Cov kev tshawb fawb tsiaj tau pom tias SS-31 kev kho mob txhim kho lub cev kev ua haujlwm, txo cov cellular puas, thiab ua rau muaj hnub nyoog cuam tshuam txog kev ua haujlwm tsis zoo (Szeto & Liu, 2018).

Rau cov tib neeg txaus siab rau kev laus noj qab haus huv, SS-31 sawv cev rau qhov tseem ceeb ntawm kev tshawb fawb tseem ceeb- lub tswv yim muaj peev xwm ua kom qeeb cellular aging, khaws cia mitochondrial muaj nuj nqi, thiab pab txhawb kev tiv thaiv lub hnub nyoog cuam tshuam.

SS-31 sawv cev rau ib qho ntawm mitochondria zoo tshaj plaws - tsom peptides tam sim no tab tom tshawb nrhiav. Los ntawm stabilizing cardiolipin, khaws cia mitochondrial membrane kev ncaj ncees, txo ROS ntau lawm, thiab tswj ATP synthesis, nws muaj peev xwm kho tau dav thoob plaws ntau yam kab mob uas muaj hnub nyoog.

Nws cov ntawv thov hauv cov leeg pob txha atrophy, Alzheimer's disease, mob plawv, thiab kev laus noj qab haus huv qhia nws qhov tseem ceeb hauv kev hloov pauv ntawm cov tshuaj mitochondrial.

Txawm hais tias SS-31 tseem nyob hauv kev soj ntsuam kuaj mob thiab tseem tsis tau txais kev pom zoo dav dav rau kev siv tshuaj kho mob niaj hnub, kev tshawb fawb tsis tu ncua tseem txhawb nqa nws lub peev xwm los ua cov tswv yim kho tshiab rau kev txhim kho mitochondrial kev noj qab haus huv thiab txuas ntxiv kev noj qab haus huv.

Cov ntaub ntawv

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Head, E., Zicker, SC, & Liu, J. (2019).Cov teebmeem ntawm SS-31 ntawm kev noj qab haus huv mitochondrial hauv Alzheimer tus kab mob qauv.Neurobiology of Aging, 76, 100–109. https://doi.org/10.1016/j.neurobiolaging.2019.06.021

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Li, J., Wang, Z., Liu, Y. (2019).Cov txiaj ntsig ntawm cov hlab plawv ntawm mitochondria- phiaj xwm antioxidant SS-31 hauv cov qauv kab mob plawv.Phau ntawv Journal of Cardiology, 32(4), 455–464. https://doi.org/10.1016/j.jcard.2019.02.015

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