
apoptosome

apoptosis prakriyayil roopappedunna oru valia quaternary protein gadanayaanu apoptosome. aantharika (aantharika) allengil baahya (baahya) kosha marana uthejakathinu marupadiyaayi maittokondriyayil ninnu cytochrome sii purathuvidunnathiloodeyaa athinte roopeekaranam aarambhikkunnath. dna kedupaadukal, vairal anubadha muthal taadpolinte wall kshayichupokunnathilekku nayikkunna vikasana soochanakal vare uthejakangal vyathyaasappedaam.
sasthanikalude koshangalil, cytochrome sii purathuvannaal, athu oru apoptosominte roopeekaranam sugamamaakkunnathin cytosolic protein apaf-1-maayi bandhippikkunnu. apoptosome roopeekaranathinu cytochrome sii-yude rund muthal oru anupatham vare apoptosome roopeekaranathinu rund muthal onnu vare anupatham undennu oru aadyakaala biochemical patanam soochippikkunnu. ennirunnaalum, sameepakaala gadanaaparamaaya padanangal soochippikkunnathu cytochrome sii-umm apaf-1 anupaathavum onnu muthal onnu vareyaanu. moonnaamathe gadakamenna nilayil nucleotide daatp apaf-1-maayi bandhippikkunnuvennum theliyikkappettittund, ennirunnaalum athinte krithyamaaya punk ippozhum charcha cheyyappedunnu. sasthanikalude apoptosominu orikkalum christalise cheythitilla, ennaal 2002 ll cryogenic transmission electron microscopy vazhi oru manushyante apaf-1/cytochrome-sii apoptosominte chithram kuranja (2 enm) resolutionil chithreekarikkukayum 7 madangu samamithiyulla heptaamerik wheel polulla kanika velippeduthukayum cheythu. aduthide, manushya apoptosominte oru idatharam resolution (9.5 Ångstrom) ghadana cryo-electron microscopy vazhi pariharikkapettu, ithu ellah apaf-1 domainukaludeyum (card, enbark, dablyudi 40) cytochrome sii ennivayude sthaanangalkku vyakthamaaya anumaanam anuvadikkunnu. monomeric, nishkriyamaaya apaf-1 sabyoonittinte (pii. dii. bii 3ezz. eph. isad) oru kristtal ghadanayum ippol undu.
roopappettukazhinjaal, apoptosominu nishkriyamaaya proo-caspace-9 neey recruit cheyyaanum sajeevamakkaanum kazhiyum. sajeevamaakkikkazhinjaal, eee iniishyettar caspacinu ifakttar kaaspesukal sajeevamakkaanum apoptosisilekku nayikkunna sambhavangalude oru cascade trigger cheyyaanum kazhiyum.
charithram.
apoptosomes allengil mitocondriya apoptosisile bii. sii. ell-2 kudumba proteinukalude punk enna yoshihid sujimoto 1998 leeii prabandhathilaanu apoptosome enna padam aadyamaayi avatharippichathu.". ennirunnaalum, apoptosome eee samayathinu munbu oru tritala samuchayamaayi ariyappettirunnu. eee samuchayathil caspace-9, bii. sii. ell-ex. ell enniva ulppedunnu, avaa oronnum oru prathyeka apaf-1 domainine bandhippikkunnu. eee samuchayathinte roopeekaranam sasthanikalude koshangalude maranathil oru niyanthrana punk vahikkumennu vishwasikkappettirunnu. athe varsham desemberil, proxpace-9 sajeevamaakkunnathiloode apoptosisinte niyanthrakan apaf-1 aanennu prasthaavikkunna oru lekhanam koodi jenal oof biological kemistriyil puratthirangi.
1999laanu apoptosominte maanadandangal nischayichathu. onnamathaayi, athu oru valia samuchayamayirikkanam (13 laksham daltonil kooduthal). randaamathaayi, athinte roopeekaranathinu eiii. tii. pii allengil daattippinte uyarnna oorjja bandhatthinte jalavishleshanam aavasyamaanu. avasaanamaayi athu proxaspace-9 athinte pravartthana roopathil sajeevamaakkanam. eee samuchayathinte roopeekaranam thirichuvaraanulla pooyintalla, apoptosis sambhavikkum. sthirathayulla apaf-1, cytochrome multimeric complexes enniva eee vivaranathinu anuyojyamaanu, ippol ithine apoptosome ennu vilikkunnu.
rund kaaranangalal apoptosome oru multimeric complexaayi kanakkaakkappettirunnu. onnamathaayi, onniladhikam procaspace-9 thanmathrakal pilarppinaayi orumichu konduvarika. randaamathaayi, apoptosisinulla paridhi uyarthaan, athinaal cytochrome sii yude nirddishtamallaatha chorcha apoptosisilekku nayikkilla.
apoptosome procaspace-9 aaktivettaraayi sthaapithamaayukazhinjal, eee paathaykkullile mutationukal oru pradhana gaveshana mekhalayaayi maari. manushyarile rakthaarbudakoshangal, andashaya arbudam, vairal anubadhakal enniva chila udaaharanangalil ulppedunnu. eee paathayude nilavile gaveshana mekhalakal kooduthal vishadamaayi charcha cheyyum. apoptosomil ninnu swathanthramaaya, koshamaranathinu maranjirikkunna vazhikalum undu, athinaal avaa apoptosomil ninnu swathanthramaanu. eee vazhikal caspace-3,9 ennivayil ninnu swathanthramaanu. apoptosisinulla eee maranjirikkunna vazhikal mandagathiyilullathaanu, pakshe kooduthal gaveshanathiloode upayogapradamaayekkaam.
ghadana.
mitocondria-mediated apoptosisine aspadamaakki adapter protein apaf 1 (apoptotic protees activating factor 1) nuu chuttum othucherunna oru multimolecular holoensime complexaanu apoptosome, ithu eathenkilum tharatthilulla stress signal vazhi uthejippikkanam. apoptosominte roopeekaranathinu cytosolil eiii. tii. pii/daatt, cytochrome sii ennivayude saannidhyam aavasyamaanu.
oru stress stimulasinu cytochrome sii cytoplasathilekku puratthuvaraan kazhiyum, athu onniladhikam dablyudi-40 aavarthanangal adangiya oru pradeshathinullil apaf-1 nte sii-terminesumaayi bandhippikkum. apaf-1nte oligomerisation, apaf-1 enn-terminasile card motifilekku proxpace-9-nte samanvayippicha recruitmentinoppam undakunnathaayi thonnunnu. apoptosisinte aantharika pathayil kaaspesukale sajeevamaakkunnathin apoptosome kaaranamaakunnu.
apoptosominte ezhu madangu samamiti gadanayulla chakraakrithiyilulla heptaamerik complexes aadyamaayi velippeduthiyathu electron chryomicroscopy teknikkukal 27 Â resolutionil aanu, koodaathe ekadesham 1 mda (achan thudangiyava) kanakkakkiya pindavumundu. 2002). eee chakram polulla kanikaykku ezhu spokkukalum oru kendra kendravumundu. speekkinte vidoora pradeshathinu oru vyakthamaaya y aakruthiyundu. oru valanja kaikondu hubb domaine vaii domainumaayi bandhippichirikkunnu. oro vaii domainilum rund lobukal (oru valiathum oru cheriyathum) adangiyirikkunnu, avaykkidayil cytochrome sii binding sittukal undu. apoptosome gadanayude resolution thaarathamyena kuravaayathinaal, apoptosome assemblic rund vivaada maathrkakal nirddeshikkappettu. oru model soochippikkunnathu nooad domainukal central hubb roopeekarikkukayum card domainukal nooad mekhalayude mukalil oru freer ring roopappeduthukayum cheiyunnu. mattoru model nirddeshikkunnathu enn-terminal card nucleotide binding mekhalayum apoptosominte kendra kendramaayi maarunna vidhathil vipulamaaya reethiyilaan apaf-1 krameekarichirikkunnathe, athesamayam 13 dablyudi-40 aavarthanangal rund lobukalaayi maarunnu. ezhu aavarthanangaliloode valia loob roopappedukayum aarr aavarthanangaliloode cheria loob roopappedukayum cheiyunnu. oro caspace-9 thanmathra kendra kendratthil oru card domaine bandhippikkukayum oru thaazhikakkudatthinte aakruthiyilulla ghadana roopappeduthukayum cheiyunnu. human apoptosome-procaspace-9 card complexinte sameepakaala hye resolution gadanayaanu eee vivaadam pariharichathu. apoptosominte kendra kendram nooad pradeshangal maathramaan roopappeduthunnathennu eee ghadana vyakthamaayi theliyichu (chithrangal kaanuka), athesamayam card apoptosominte plaattfomumaayi vazhakkathode bandhippichirikkunnu, koodaathe graundu stettu apoptosomil kramarahithamaakunnu. apoptosome proxaspace-9-maayi bandhichukazhinjaal, apaf-1 kaardukalum proxaspace-9 kaardukalum platfominu mukalil irikkunna oru flexible disk polulla ghadana roopappeduthunnu. dablyudi-40 aavarthanangalude ennavum 13 nuu pakaram 15 aanennu theliyikkappettittund, ithu 7-blade beetaa-propeller 8-blade beetaa-propeller chernnathaanu.
complexinullile proxaspace-9-nteyum apaf-1-nteyum stokkiyometrik anupatham ekadesham 1:1 aanennu vaangil ninnum sahapravarthakaril ninnumulla thelivukal soochippikkunnu. kvaanditteevu maas spectrometry vishakalanathiloode ithu kooduthal theliyikkapettu. samuchayathinullile cytochrome sii muthal apaf-1 vareyulla stokkiyometri 1:1 aanennu theliyikkappettittund. oligomeraiseshanethudarnnu apoptosomilake cytochrome sii sthiramaayi samyojippikkendathundo ennathinekkurichu chila samvaadangalundu, ennaal cytochrome sii oligomeric human apoptosomine sthirappeduthunnu enna ashayathe sameepakaala gadanaaparamaaya daatta anukoolikkunnu. ennirunnaalum, puzhukkalum pazha eechakalum polulla sasthanikalallaatha enangalil apoptosominte samyojanathinu cytochrome sii aavashyamaayi varilla. koodaathe, mattu niravadhi thanmathrakal, prathyekichu caspace-3, apoptosomumaayi saha-shudheekarikkunnathaayi report cheyyappettittund, caspace-3 nuu apoptosome-procaspace-9 complexine bandhippikkaan kazhiyumennu theliyikkappettittund.
apoptosominte nattellaan apaf-1. ithinu moonnu vyathyastha mekhalakalunda enn-terminal caspace-recruitment domaine (card, avashishtangal <aii. dii. 1>), oru central nucleotide-binding, oligomerisation reejian (enn. bii.-aarr. sii/nooad, <aii. dii. 3>), sii-terminal dablyu. dii. 40 reejian (<aii. dii. 2>) enniva ekadesham 140 keey. dii. eiii protein undaakkunnu.
samrakshitha wacker boxukal adangiya eiii/bii domainukale (enbidi) bandhippikkunna oru hraswa linker nucleotide enn-terminal card domainine pinthudarunnu. daatt/atp, emji2 + bindinginu wacker boxukal eiii/bii nirnaayakamaan. enn. bii. dii. kku sesham oru cheria helical domaine (echu. dii. 1), randaamathe linker, samrakshitha chirakukalulla helix domaine (dablyu. echu. dii) ennivayundu. nooad mekhalayil enbidi, echdi 1, doubleuechdy enniva ulppedunnu, ithu aaa + kudumbatthinte atpesukalude bhagamaaya oru atpes domaine srishtikkunnu. nodinum dablyudi-40 aavarthanangalkkumidayila junctionil oru suuppar helical domaine (echdi 2) undu. dablyudi 40 aavarthanangal ettu, ezhu grouppukalilaayi linkerukal bandhippichirikkunnu.
mattu jeevajaalangalile apoptosomukal.
melpparanja vivaranagal manushya apoptosominu vendiyullathaanu. mattu jeevikalil ninnulla apoptosome sankeernna gadanakalkku niravadhi samaanathakalundengilum chithratthil kaanichirikkunnathupole avaa valare vyathyastha valuppathilum upaghadakangalude ennathilumaanu. dark ennu vilikkunna fruit-fly systethinu 8 sabyoonittukalude (pii. dii. bii 4vii4ell) oru valayamundu. sedu-4 ennu vilikkunna nemattod apoptosome oktamerik aanenkilum valare cheruthaanu (pii. dii. bii 3ell. kyu. kyu), cytochrome siye bandhippikkunna pradeshangal ithil ulppedunnilla.
pravartthana samvidaanam.
thudakkamidunnu.
 apoptosome pravartthanatthinte arambham prograam cheytha sell deth (pcd) paathayile aadya ghattangalumayi poruthappedunnu. mrugangalil, apoptosis rund vazhikalilonnil uthejippikkaan kazhiyum; extra sellular ligaandukale transmembran resepterukalumaayi bandhippikkunnath extra sellular pathayil ulppedunnu, athesamayam aantharika paatha mitocondriyayilaanu nadakkunnathu. eee aantharika pathayil maittokondriyayil ninnu cytochrome sii purathuvidunnathum thudarnnu cytosolic protein apaf-1-maayi bandhippikkunnathum ulppedunnu. athinaal apoptosome pravartthanatthinte thudakkathinu cytochrome sii release aavasyamaanu; eee release niravadhi vazhikalil niyanthrikkappedunnu, ettavum pradhanamaayi kaalsyam ayoninte alavu kandethunnathiloode.
cytochrome sii release.
cytochrome sii release rund vazhikalil onnil nadatthaan nirddeshikkappedunnu. onnamathaayi, mitocondriaykku maranathe prerippikkunna signal labikkukayum intermembran space proteinukal purathuvidukayum cheyyumbol permiability transition pore (pidipi) (12). volteju-dependent ayoon chaanal (vdac), innar membran protein adenine nucleotide translockettar (adnt), matricks protein cyclophiline dii (side) (12) enniva chernnathaanu pidipi. eee sushirangal mitocondria veengunnathinum puram mitocondrial membron pottunnathinum kaaranamaakunnu (diamond & mccabe, 2007). paaragamyathayile eee maattathode, cytochrome sii polulla proteinukal cytosolilekku purathuvarunnu (12). eee maattam mitocondrial paragamyatha parivarthanatthinu (emm. pii. tii) kaaranamaakunnu, avide mitocondrial transmembran pottensial thakarukayum eiii. tii. pii uthppaadanam avasaanikkukayum cheiyunnu (12). farmaceutical ejantu cyclosporin eiii (csa) eee reethi thadayunnathu randaamathe paathayude kandethalilekku nayikkunnu (13). cytochrome sii releasile randaamathe reethi pidipiyil ninnu swathanthramaanu, athil vdsil maathram ulppedunnu. proo-apoptotic proteinukalude bii. sii. ell-2 kudumbatthile amgangalkku vii. dii. eiii. sii. (12) thurakkaan kazhiyum. ithu cytochrome sii ulppedeyulla intermembran space proteinukalude athe prakaashanatthinum thudarnnulla emm. pii. tii. yum (12) sambhavikkaan kaaranamakum.
apaf-1.
eiii. cytochrome sii yude abhavam.
 cytochrome sii yude abhaavathil, apaf-1 athinte monomeric roopathil nilanilkkunnu; dablyudi-40 domaine proteinilekku madakki vaykkukayum, apaf-1 oottoo inhibited avasthayil nilanirthukayum cheiyunnuvennu karuthappedunnu. koodaathe, proteinu mattonnumayi bandhippikkaan kazhiyaathavidham niravadhi pradeshangal valare karsanamaayi bandhippichirikkunnu. maas spectrometriyiloode autoinhibited allengil "loock cheytha" avasthayil, eiii. dii. pii. apaf-1nte atpes domainumaayi bandhappettirikkunnave nirnnayikkappettundu. eee avasthayil, eee protein ekavachanamaanu, koodaathe kaaspesukal sajeevamakkaan kazhivilla.
bii. cytochrome sii yude saannidhyam.
 cytochrome sii apaf-1nte dablyudi-40 domainumaayi bandhippikkunnu. ithu "loock" release cheyyaan anuvadikkunnu, athaayath eee domaine inii autoinhibit cheythitilla. ennirunnaalum, card enby-aarsi domainukalum autoinhibited avasthayilaanu. (dii) eiii. tii. pii/eiii. tii. piyumayi bandhippikkumbol maathrame card domaine eee loock vazhi purathuvarikayulloo; eiii. tii. pii bandhippikkumbol, card domaine caspace-9-maayi bandhippikkaan anuvadikkum. eiii. dii. pii. eiii. tii. pii. domainil aayirikkumbol, oligomerisation thadassappedum. athinaal, eiii. tii. piyude binding downstream caspace aaktiveshan cheiyunnathinu aavashyamaaya heptagonal gadanayilekku apaf-1 nte oligomerisation anuvadikkunnu. atpes domainile mutationukal proteine nishkriyamaakkunnu; ennirunnaalum, eee eiii. dii. pii-eiii. tii. pii exchange niyanthrikkunnathinulla reethi vyakthamalla.
 athinaal 7 cytochrome sii thanmathrakal, 7 apaf-1 proteinukal, mathiyaya (dii) atp/atp ennivayude saannidhyathil maathrame oligomerisation sambhavikkoo. atpes domaine AAA + kudumbatthile atpesukalil pedunnu; mattu atpes domainukalumaayi bandhippikkanum hexa allengil heptaamarukal roopeekarikkaanumulla kazhivinu eee kudumbam ariyappedunnu. oru chakrakhadanayil krameekarichirikkunna ezhu apaf-1 thanmathrakal, enby-aark domainukal kendratthil vishramikkunna tharatthil ooriyantad cheyyumbol apoptosome sajeevamaayi kanakkaakkappedunnu.
sajeevamaaya apoptosome pravartthanam.
eee pravarthanakshamamaaya apoptosominu caspace 9-nte oru plaattphom aaktiveshan nalkaan kazhiyum.
cytosolil oru saimojanaayi nilanilkkunna caspace 9 koshangalil 20 enn. emm. ll kaanappedumenn karuthappedunnu. sajeevamakaan saimojan pilarthenda aavasyamillennu ariyaamenkilum, pilarnnukazhinjaal proxpace-9 nte pravartthanam ganyamaayi vardhikkaam. aadyathe sidhaantham villalin munbu rund caspace 9 thanmaathrakalude dimerisation nadatthaan apoptosome oru sthaanam nalkunnu ennathaanu; eee sidhaantham 2007 ll reedle & salvassen anukoolamaayirunnu. randaamathethu caspace 9 athinte monomeric roopathil aayirikkumbol villal sambhavikkunnu ennathaanu. oro kesilum, caspace 9 aaktiveshan oru poornna caspace cascade aaktiveshan cheiyunnathilekkum thudarnnulla sell maranathilekkum nayikkunnu. caspace cascade sajeevamaakkunna multimeric protein complexinte parinaama kaaranam cytochrome siyude alavu abadhathil apoptosisinu kaaranamaakunnillenn urappaakkuka ennathaanu.
gaveshana mekhalakal.
mutationukal sambhavikkumbol enthaanu sambhavikkunnath?
shareerathinte swaabhaavika pravarthanatthinu apoptosis aavashyamaanenkilum, apoptosome paathayude mutationukal shareerathil vinashakaramaaya phalangalum maattangalum undaakkunnu. kosha paathayude mutationukal onnukil koshangalude maranathe prothsaahippikkukayo shareerathil valia alavil rogangal srishtikkunna koshangalude maranathe anuvadikkaathirikkukayo cheyyum. apoptosome pravartthanatthinte abhavam, amithamaya apoptosome pravartthanam moolamulla alsheimer rogam, paarkkinsans rogam, huntingtons rogam thudangiya mattu niravadhi neuro degenerative rogangal enniva kaaranam cancer muthal rogamundaakkunna parivartthana apoptosis pathakal daaraalamundu. alsheimer, paarkkinsans, huntingtons thudangiya neuro degenerative rogangalellaam praayavumaayi bandhapetta rogangalaanu, koodaathe koshangal ippozhum pravartthikkaan kazhiyunnatho tissuevinte pravartthanatthe pinthunaykkunnathinu sambhavana cheiyunnatho aaya koshangal marikkunna apoptosis vardhikkunnu. prostettu canceril kaanapedunna oru apaf-1 myoottantaan apaf-1-alt, athil avashishtangal 339-1248 illa. apoptosominte sameepakaala gadanaaparamaaya padanangal theliyikkunnathu apaf-1-altinu apoptosome roopappeduthaan kazhiyillennu kaaranam asambliyude pradhana gadanaaparamaaya gadakangal nashtappedunnu.
apeptosis adichamarthal cancerinu kaaranamaakunnu.
oru koshatthinullile janithaka, biochemical asaadhaaranathakal saadhaaranayaayi kramamillaatha kosha pravartthanatthil ninnum vikasanathil ninnum shareerathe mochippikkunnathinu prograam cheytha kosha maranathinu kaaranamaakunnu; ennirunnaalum, cancer koshangal apoptosis adichamarthaanum athijeevikkaanum anuvadikkunna mutationukal nediyittundu. saadhaarana pii. sii. dii. prolsaahippikkunnathi hyper-stimuleshan vazhi eee adichamarthappetta pii. sii. dii. pathakal sajeevamaakkunnathin ionizing radiation polulla chemotherapykal vikasippichittund.
apoptosisile pii53 mutationukal.
kyaansar thadayunnathil earppettirikkunna tumour saprassaraayi pii53 pravartthikkunnu, ithu apoptotic pathakalil swaabhaavikamaayi sambhavikkunnu. p53 koshangal apoptosisilekku praveshikkukayum kooduthal kosha vibhajanathe thadassappeduthukayum cheiyunnu, athinaal aaa koshatthe cancer aakunnathil ninnu thadayunnu (16). mikka arbudangalilum pii53 paathayaan parivartthanam cheyyappettathu, athinte falamaayi pravarthanarahithamaaya koshangale avasaanippikkanulla kazhivu illa. deerghakaalam jeevikkunna mrugangale uthppaadippikkunna pii53 jeeninte mutationukal aadhipathya-negatteevu roopangalude aavishkaarathin kaaranamakunna parimithamaaya ayuss kaalayalavinum pii53 function kaaranamakum. udaaharanathinu sii upayogichulla oru pareekshanatthil. elegans, pii53 myoottantukalude vardhicha ayuss vardhicha autofaagiye aashrayichirikkunnuvennu kandethi. drosophila upayogicha mattoru pareekshanatthil pii53 mutation muthirnnavarude aayussil positteev, negatteevu efakttukal undaakki, ithu laingika vyathyasam, pcd, vaardhakyam enniva thammilulla bandhathe nigamanam cheythu. pii53 aayurdairkhyathe engane baadhikkunnuvenn nirnnayikkunnath bhaaviyile gaveshanathinu oru pradhana mekhalayayirikkum.
cancer chikilsaykkaayi apoptosomine lakshyamidunnu.
apoptosis thadayunnathu kaansarinte pradhana savisheshathakalilonnaanu, athinaal apoptosome roopappeduthunnathinum kaaspesukal sajeevamakkunnathinum eee nirodhanam kaikaaryam cheyyaanum marikadakkaanumulla vazhikal kandethunnathu puthiya cancer chikilsakalude vikasanathil pradhaanamaan. cancer chikilsayil apoptosome sajeevamakkaanulla kazhivu vilappettathaan, kaaranam rogabadhithamaaya cancer jeenukal nasippikkaan kazhiyaathathinal cancer roopappedunnathu thudarunnu. oru baahya uttejaka apoptosis vazhi apoptosome sajeevamaakkunnathiloode sambhavikkukayum parivartthana koshangalil ninnu mukti nedukayum cheyyaam. manushyarogangalile amithamo kuravo aaya koshamaranam pariharikkunnathinulla sameepanathil nirddishta apoptotic regulatormaare lakshyamidunnathinaayi recombinent biomoleculeukal, antisense thanthrangal, jeane therapy, classic oorgaanik kompinettoriyal kemistry ennivayulppede niravadhi sameepanagal nilavil pinthudarunnu.
pothuve aanti-apoptotic proteinukalude uyarnna niyanthranam inhibittarukal vazhi pariharikkan kazhiyunna apoptosis thadayunnathilekku nayikkunnu, koodaathe aanti-apoptotic proteinukalude daun regulation apoptosis inductionilekku nayikkunnu, ithu avayude pravartthanatthe bandhippikkanum parishkkarikkanum kazhiyunna aaktivettarukal vazhi vipareethamaakunnu. apoptosis adisthaanamaakkiyulla chikilsakalil oru pradhana taargett molecule marunninte roopakalppanaykkulla bii. sii. ell-2 aanu. kyaansar thadayunna apoptosisinu kaaranamakunna aadyathe oongoojen aanu bii. sii. ell-2. ithu tumourukalil amithamaayi prakadippikkukayum chemotherapy prathirodhikkukayum cheiyunnu. bii. sii. ell-2 aanti-apoptotic proteinukalumaayi depressorukale bandhippikkunnath avaye thadayunnuvennum baiks, bake ennivayumaayi samvadikkaan nerittulla aaktivettarukale swathanthramaakkunnuvennum shaasthranjar kandethi.
cancer therapic lakshyamidunna mattoru thanmathrayil caspace kudumbavum avayude niyanthranakkaarum ulppedunnu. neuro degenerative disordezhs, strock, hridayaaghaatham, karal parikk ennivayulppedeyulla manushyarogangalil koshangalude maranathe caspace pravartthanam thadayunnu. athinaal, strockin mattu manushyarogangalkkum chikitsa nalkunna oru mikacha pharmacological upakaranamaan caspace inhibittarukal. chila neuro degenerative rogangalude vipareeta phalangalude vaagdaanaparamaaya thelivukal kaanikkunna niravadhi caspace inhibittarukal nilavil preclinical ghattathilaanu. aduthide nadatthiya oru padanatthil gaveshakar emm-826 enna reversible caspace-3 inhibittar vikasippikkukayum athu mastishka koshangalude kedupaadukal thadayunna mouse modalil pareekshikkukayum cheythu. koodaathe, huntingtons rogamulla oru eliyil ithu pareekshikkukayum eee caspace inhibittarinekkurichu kooduthal padanatthinu prateeksha nalkunna phalangal velippeduthunna straittad neuron maranam inhibittar thadayukayum cheythu.
apoptosome complexes molecular therapic saadhyathayulla puthiya lakshyangal velippeduthi.
apoptotic cascadil nirnayakamaaya oru sambhavamaan apaf 1/caspace-9 apoptosome roopeekaranam. sajeevamaaya apoptosome complexinte roopeekaranam thadayukayo sthirappeduthukayo cheiyunna puthiya saadhyathayulla marunnukal thirichariyunnathu amithamo aparyaapthamo aaya apoptosis swabhaavamulla rogathinte chikilsaykku anuyojyamaaya thanthramaan. mitocondrial pravarthanakshamatha thadayaathe apaf 1/caspace-9 apoptosome roopeekaranam thadayaanulla kazhiviloode cardiomyocytukalile ischemia-induced apoptosis thadayaan tourin aduthide kandethiyittundu. apoptosominte roopeekaranathe thadayunna torin saadhyamaaya samvidaanam apoptosominte adisthaana gadakamaaya caspace-9nte aavishkaaram kuraykkaan kazhivullathayi thiricharinju. ennirunnaalum, apoptosome ozhikeyulla swathanthramaaya punk apaf 1, caspace-9 ennivaykku undennu kaanikkunna padanangalundu, athinaal avayude alavil maattam varuthunnathu koshatthinte pravartthanatheyum mattiyekkaam. athinaal pareekshanathmaka daattaye prothsaahippichenkilum niravadhi prasnangal pariharikkappedaathe thudarukayum klinikkal praakteesil pareekshanathmaka marunnukalude upayogam parimithappedutthukayum cheiyunnu.
apoptosome inhibittarukal kandethunnathu apoptosis mediated rogathinte chikilsaykkaayi oru puthiya chikitsa upakaranam nalkum. apoptosome gadakangalude transcriptional nilakalil maattam varuthaathe intra sellular protein-protein edapedalukalil pravartthikkunnathiloode apoptosome sthirathayum pravartthanavum thadayaan kazhiyunna puthiya samyukthangalkk prathyeka praadhaanyamund. apoptosominte sameepakaala gadanaaparamaaya padanangal apoptosome adisthaanamaakkiyulla chikilsakal roopakalppana cheiyunnathinu vilapetta upakaranangal nalkiyekkaam.

