Ukuthintela ukusasazwa kwe-alpha-synuclein nge-perampanel

[00:01:13] UDkt. Norihito Uemura:
Izifo zomzimba zeLewy zibonakaliswa kukusasazeka kwe-alpha-synuclein pathology engaqhelekanga ngengqondo. Ubungqina obuqokelelweyo kwizifundo zovavanyo lwesidumbu kunye neemodeli zezilwanyana bubonisa ukuba le pathology isasazeka kwimijikelezo ye-neural ukusuka kwenye i-neuron ukuya kwenye i-neuron. Le nkqubo siyibiza ngokuba yi-trans-synaptic propagation, kwaye kusenokwenzeka ukuba ibandakanya ukukhululwa kunye nokufunxwa kweentlobo ze-alpha-synuclein ezibangela izifo.

Ngenxa yokuba le nkqubo kucingelwa ukuba iqhuba ukuqhubela phambili kwesifo, sikholelwa ukuba imele injongo ekhangayo yonyango oluguqula isifo.

[00:01:56] UProf. Tiago Outeiro:
Ewe. Kuhle kakhulu. Ngoko ke kumsebenzi wangaphambili weqela lakho, ubonise ukuba i-perampanel, eyi-AMPA receptor antagonist, inokuthintela ukufunxwa kwe-alpha-synuclein preformed fibrils kwi-neurons ngokuxhomekeke kwimisebenzi. Ngoko ke yeyiphi imibuzo ephambili evulekileyo kumsebenzi wakho wangaphambili eyakhuthaza olu phando lutsha?

[00:02:18] UDkt. Norihito Uemura:
Kwisifundo sethu sangaphambili sibonise ukuba i-perampanel ithintela ukuthathwa kwe-alpha-synuclein fibers kwi-neuron ezikhuliswe kakuhle kunye neengqondo zeempuku. Nangona kunjalo, bekungekacaci ukuba ukuthintela inyathelo lokuqala lokuthathwa kuya kuyithintela na i-trans-synaptic spread of pathology elandelayo kuyo yonke ingqondo.

Ngamanye amazwi, iindlela zokuthathwa kweefayibha kwi-neuron zinokwahluka kwindlela ye-pathological yokudluliselwa kwe-alpha-synuclein kwi-neuron. Le yinkuthazo yophando lwangoku.

[00:03:03] UProf. Tiago Outeiro:
Ngokuphathelele indlela yokusebenza, enye yezinto eziphambili ezifunyenweyo yayikukuba ukuthathwa kwe-alpha-synuclein fibrils kwi-neuronal kuxhomekeke kwi-dynamin kodwa akuxhomekekanga kwi-clathrin, kwaye i-perampanel yonyusa amanqanaba e-dynamin I e-phosphorylated in vivo. Ngoko ke oku kunzima kancinci kubaphulaphuli bethu kuba ezi ziinkqubo ze-molecular ezineenkcukacha ezininzi.

Ngoko ke, ungachaza ngokufutshane indlela otolika ngayo ezi ziphumo ngendlela yokusebenza, kwaye zisixelela ntoni ngeendlela ezithile ze-endocytic ezisingatha i-alpha-synuclein? Le yindlela evumela ukuba iproteni ithathwe yiseli. Ngoko ke ngendlela yokusebenza, singacinga njani ngeziphumo zakho?

[00:03:47] UDkt. Norihito Uemura:
Ewe. Kolu phononongo lwangoku siyazi ukuba i-endocytosis exhomekeke kwi-dynamin inxulunyaniswa ngokusondeleyo nokusasazeka kwe-alpha-synuclein pathology engqondweni. Kwaye oku kufunyanisiweyo kwandisa injongo yethu yonyango kwizifo zomzimba waseLewy. Enyanisweni unyango lwe-perampanel lonyuse i-phosphorylated dynamin kwiingqondo zeempuku. Oku kuthetha ukuba i-perampabel ikwavale i-endocytosis exhomekeke kwi-dynamin kwiingqondo zeempuku.

Oku kubaluleke kakhulu ekufumaneni kwethu oku

[00:04:24] UProf. Tiago Outeiro:
Ewe. Kulungile. Ngoku ke ukuba siya kwiziphumo zokuziphatha ezisinika umbono ongcono wempembelelo kwinqanaba le-physiological. Unyango olusebenzisa i-perampanel kuphando lwakho luvelise ukungasebenzi kakuhle, ukuziphatha okufana nokuxhalaba, kunye nokuncipha kobunzima obunokuthi mhlawumbi ubungalindelanga.

Ngoko ke oogqirha bafanele bacinge njani ngezi ziphumo ebezingalindelekanga xa becinga nge-perampanel okanye ezinye izichasi ze-AMPA njengezinto eziguqula isifo? Ngoko ke siyazi ukuba unefuthe ekusasazeni, nto leyo ibalulekileyo, kodwa ke uneziphumo ebezingalindelekanga kunye neziphumo zokuziphatha. Ngaba ucinga ukuba oku kufanele kukhathaze oogqirha ngandlela ithile kangangokuba sifanele siqwalasele ezi nguqu.

[00:05:11] UDkt. Norihito Uemura:
Enyanisweni, ewe, oko kungumda wolu phononongo. Kodwa nangona oku kunqongophala, i-perampanel sele isetyenziswa njengonyango lwesifo sokuwa kwaye ineendlela zonyango ezikhuselekileyo ezisele zikho. Isiphumo esibi sinokubonakala, isiphumo esibi sinokwahluka phakathi kweemodeli zezilwanyana nabantu. Kwaye into endifuna ukuyigxininisa kukuba uluhlu lonyango olukhuselekileyo sele lukhona ebantwini. Ndicinga ukuba nangona esi siphumo sibi kwiimodeli zegundane, singacinga ngokutshintshela kuvavanyo lweklinikhi nge-perampanel.

[00:05:54] UProf. Tiago Outeiro:
Hayi, oku kunomdla kakhulu kwaye bendiza kuqwalasela oku kusetyenziswa kwe-perampanel kwisifo sokuwa. Njengoko ubutshilo, kunye noluhlu lweedosi ezimiselweyo ukuze sazi ukuba zeziphi iidosi ekufuneka zisetyenziswe ebantwini. ngoko ke ucinga ukuba singakwazi ukufumana ubungqina kwizigulana eziye zanyangwa nge-perampanel ukuba umntu angafikelela kwiingqondo zakhe ukuze abone ukuba kukho na impembelelo kwi-pathology ye-alpha-synuclein?

Andazi ukuba kukho ubuchopho obukhoyo na, kodwa ukuba besinokufikelela kwiingqondo ezivela kwizigulana ezinyangwe nge-perampanel, mhlawumbi besinokubona ubungqina obuthile bempembelelo ekusasazeni ukwanda kwe-synuclein. Mhlawumbi oku kungaba luncedo.

[00:06:38] UDkt. Norihito Uemura:
Ngokwazi kwam bekukho uphando olunye olugxile kunyango lwe-perampanel lokuguguleka kwesifo sikaParkinson. Kodwa olo phononongo lutyhile ukuba i-perampanel ayisebenzi ekugugulekeni kwesifo sikaParkinson. Andazi ukuba ngokwazi kwam, akukho ngxelo ijonga ukusebenza kwe-perampanel ekusasazekeni kwe-alpha-synuclein.

[00:07:04] UProf. Tiago Outeiro:
Ewe, ngoko ke kuninzi ekufuneka kwenziwe. Oko kucacile, kwaye kulungile kuba, yindlela esebenza ngayo isayensi. Ngoko ke ucinga ukuba ngawaphi amanyathelo alandelayo eqela lakho, mhlawumbi sele usebenza kuwo ukuze ulandelele iziphumo zakho? Ngawaphi imibuzo elandelayo?

[00:07:20] UDkt. Norihito Uemura:
Ewe. Nangona uphando lunomda, njengoko benditshilo ngesiphumo esibi kwiimodeli zeempuku, sicinga ukuba singaya kuvavanyo lweklinikhi nge-perampanel kwisifo sikaParkinson. Olunye uphando olunokwenzeka oluhambelana nolu phononongo lweempuku.

Olunye uvavanyo lwezonyango olunokwenzeka kukuba lugxile kwizigulane zesifo sikaParkinson ezine-hyposmia. Izifundo ezininzi zangaphambili zibike ukuba izigulane zesifo sikaParkinson ezine-hyposmia zinomngcipheko ophezulu wokuba ne-dementia xa kuthelekiswa nezigulane zesifo sikaParkinson ezingenayo i-hyposmia.

Sicinga ngovavanyo lweklinikhi lokusebenza kwe-perampanel ngokuchasene nokukhula kwe-dementia kwizigulane ezine-hyposmia ngenxa yesifo sikaParkinson.

[00:08:12] UProf. Tiago Outeiro:
Kulungile. Ngoko ke, loo nto ingaba liqela labantu apho uvavanyo luya kuba nengqiqo. Ngoko ke sifikelele esiphelweni, ngoko ke ndingathanda ukukubuza, ngaba kukho enye into ongathanda ukuyigxininisa malunga nesifundo sakho? Ngaba kukho into esingakhange siyithethe? Ngaba kukho nto ibalulekileyo ongathanda ukuyithetha.

[00:08:27] UDkt. Norihito Uemura:
Into endifuna ukuyigxininisa kukuba olu phononongo alupheleli kwiyeza elinye kuphela. Olu phononongo lutyhile ukuba singaluvavanya olo nyango luguqula izifo ngokuchasene nokusasazwa kwe-alpha-synuclein kwimodeli zeempuku.

Ngale ndlela, singavavanya amanye amayeza anokubakho ukuvavanya ukusebenza kakuhle ngokuchasene nokusasazeka kwe-alpha-synuclein kwi-trunk synaptic. Injongo ithembisa, kwaye ndiyathemba ukuba olu nyango lutshintshayo nxamnye nale njongo luya kufumaneka kwizifo zomzimba zaseLewy.

[00:09:06] UProf. Tiago Outeiro:
Ewe. Enkosi. Linqaku elihle kakhulu elo kuba useke imodeli enokuba luncedo kakhulu ekuvavanyeni ezinye iintlobo zeemolekyuli ukongeza. Kwaye ke ndicinga ukuba lo ngumyalezo obaluleke kakhulu ovela kuphando lwakho. Ewe, unika ingxelo nge-perampanel, kodwa ngemodeli onayo, mhlawumbi amanye amayeza anokuvavanywa, kwaye oku kunokubonakaliswa kubalulekile.

Enkosi kakhulu. Bekumnandi ukuthetha nawe nokufunda ngezinto ozifumanisileyo. Enkosi ngexesha lakho.

[00:09:33] UDkt. Norihito Uemura:
Kumnandi kakhulu ukuthetha nawe. Enkosi kakhulu

[00:09:36] UProf. Tiago Outeiro:
Enkosi. Ngoko ke sisandula udliwanondlebe noGqr. Uemura waseKyoto University kunye neOsaka Metropolitan University eJapan malunga nokupapashwa kwabo kutshanje kwiMovement Disorders. Ngoko ke enkosi nonke ngokumamela kunye nokujoyina iipodcasts zethu ezizayo.