Kuvhara kupararira kwealpha-synuclein ne perampanel

[00:01:13] Dr. Norihito Uemura:
Zvirwere zvemuviri weLewy zvinoonekwa nekupararira kwechirwere chealpha-synuclein chisina kujairika kuburikidza neuropi. Humbowo hwakaunganidzwa kubva muzvidzidzo zvekuongorora muviri uye mhando dzemhuka hunoratidza kuti chirwere ichi chinopararira kuburikidza netsinga dzetsinga kubva kune imwe neuron kuenda kune imwe neuron. Tinodana maitiro aya kuti trans-synaptic propagation, uye zvinogona kunge zvinosanganisira kuburitswa uye kutorwa kwemarudzi e alpha-synuclein ane pathogenic.

Nekuti maitiro aya anofungidzirwa kuti anotungamira kufambira mberi kwechirwere, tinotenda kuti anomiririra chinangwa chinokwezva chekurapa kunogadzirisa chirwere.

[00:01:56] Prof. Tiago Outeiro:
Ehe. Zvakanaka kwazvo. Saka mumabasa ekare kubva kuchikwata chenyu, makaratidza kuti perampanel, iyo inova AMPA receptor antagonist, inogona kudzivirira kutorwa kwe alpha-synuclein preformed fibrils muma neuron zvichienderana nemabasa. Saka ndeapi mibvunzo mikuru yakavhurika kubva kubasa renyu rekutanga yakakurudzira chidzidzo chitsva ichi?

[00:02:18] Dr. Norihito Uemura:
Muchidzidzo chedu chekare takaratidza kuti perampanel inodzivirira kutorwa kwe alpha-synuclein fibers zvichienderana nebasa retsinga dzetsinga mumasero etsinga akakura uye uropi hwembeva. Zvisinei, hazvina kujeka kana kuvharidzira danho rekutanga rekutora kwaizoderedza kupararira kwechirwere chetsinga muuropi hwese kuburikidza ne trans-synaptic.

Nemamwe mashoko, nzira dzinoshandiswa pakubata tambo dzetsinga dzinogona kusiyana nedzekushandisa nzira dzinoshandiswa pakutapurirana kwealpha-synuclein kubva kumasero etsinga kuenda kumasero etsinga. Izvi ndizvo zvinokurudzira chidzidzo chiri kuitwa pari zvino.

[00:03:03] Prof. Tiago Outeiro:
Uye maererano nemaitiro acho, chimwe chezvakawanikwa zvikuru ndechekuti kutorwa kwe alpha-synuclein fibrils mutsinga dzeuropi kunoenderana ne dynamin asi hakuenderane ne clathrin, uye kuti perampanel inowedzera phosphorylated dynamin I levels mumuviri. Saka izvi zvakaoma kune vateereri vedu nekuti idzi imota dzakanyatsotsanangurwa.

Saka munogona here kutsanangura muchidimbu kuti munodudzira sei mhedzisiro iyi nenzira yemakemikari, uye inotiudzei nezvenzira dze endocytic dzinobata alpha-synuclein? Idzi ndidzo nzira dzinoita kuti protein itorerwe nesero. Saka nenzira yemakemikari, tingafunga sei nezvezvawakawana?

[00:03:47] Dr. Norihito Uemura:
Ehe. Kubva muchidzidzo ichi chazvino tinoziva kuti dynamin-dependent endocytosis inobatanidzwa zvakanyanya nekupararira kwe alpha-synuclein pathology muuropi. Uye kuwanikwa uku kunowedzera chinangwa chedu chekurapa zvirwere zvemuviri weLewy. Kutaura zvazviri, kurapwa kweperampanel kwakawedzera phosphorylated dynamin muuropi hwembeva. Izvi zvinoratidza kuti perampabel yakavharawo dynamin-dependent endocytosis muuropi hwembeva.

Izvi zvakakosha pane zvatinowana mune izvi

[00:04:24] Prof. Tiago Outeiro:
Ehe. Zvakanaka. Uye zvino kana tikaenda kune mhedzisiro yemaitiro inotipa pfungwa iri nani yemhedzisiro yacho padanho remuviri. Kurapa neperampanel muchidzidzo chako kwakakonzera kusava nehanya, maitiro akafanana nekuzvidya mwoyo, uye kudzikira kwekuwedzera uremu izvo pamwe waizo-- zvawaisatarisira.

Saka vanachiremba vanofanira kufunga sei nezvemigumisiro iyi inogona kuitika pavanenge vachifunga nezve perampanel kana zvimwe zvinodhaka zvinorwisa AMPA senzira dzinochinja chirwere? Saka tinoziva kuti une simba pakukura kwechirwere, izvo zvakakosha, asi une migumisiro iyi uye maitiro ako. Unofunga here kuti izvi zvinofanira kunetsa vanachiremba neimwe nzira zvekuti tinofanira kufunga nezvekuchinja uku?

[00:05:11] Dr. Norihito Uemura:
Kutaura chokwadi, hongu, izvo zvidiki pane chidzidzo ichi. Asi pasinei nekudziviswa uku, perampanel yatove kushandiswa semushonga wepfari uye ine mhando dzakachengeteka dzekurapa. Mhedzisiro yakaipa inogona kuoneka yemhedzisiro yakaipa inogona kusiyana pakati pemhando dzemhuka nevanhu. Uye chandinoda kusimbisa ndechekuti mhando dzakachengeteka dzekurapa dzakatovepo muvanhu. Ndinofunga kuti pasinei nemhedzisiro iyi yakaipa mumhando dzembeva tinogona kufunga nezvekuenda kukiriniki yekuedza neperampanel.

[00:05:54] Prof. Tiago Outeiro:
Kwete, izvi zvinonakidza uye ndaida kutanga ndanzwisisa nezvekushandiswa kwe perampanel mukurapa pfari. Sezvamakataura, nematanho akatarwa ekushandisa saka tinoziva kuti ndeapi madosi ekushandisa muvanhu. Saka munofunga kuti tingakwanisa kuwana humbowo kubva kuvarwere vakamborapwa ne perampanel kana munhu akakwanisa kupinda muuropi hwake kuti aone kana paine mhedzisiro pachirwere che alpha-synuclein?

Handizive kana paine uropi huripo, asi dai taikwanisa kuwana uropi kubva kuvarwere vakarapwa ne perampanel, saka pamwe taigona kutoona humbowo hwemhedzisiro pakupararira kwe synuclein propagation. Pamwe izvi zvaizobatsira.

[00:06:38] Dr. Norihito Uemura:
Sekuziva kwangu, paiva neongororo imwe chete yaitarisa pakurapa perampanel pakupererwa nechirwere cheParkinson. Asi ongororo iyoyo yakaratidza kuti perampanel yakanga isingashande pakupererwa nechirwere cheParkinson. Handizivi kuti sekuziva kwangu, hapana mushumo unoratidza kushanda kweperampanel pakupararira kwealpha-synuclein.

[00:07:04] Prof. Tiago Outeiro:
Ehe, saka pane zvakawanda zvinoda kuitwa. Izvozvo zviri pachena, uye zvakanaka nekuti, ndizvo zvinoshanda sainzi. Saka unofunga kuti chii chingave nhanho dzinotevera dzeboka rako, pamwe uri kutoshanda pazviri kuti utevere zvawakawana? Ndeipi mibvunzo inotevera ingave?

[00:07:20] Dr. Norihito Uemura:
Ehe. Pasinei nekuganhurirwa kwechidzidzo ichi, sezvandakataura nezvemhedzisiro yakaipa mumamodeli embeva, tiri kufunga kana tichigona kuenda kuchidzidzo chekiriniki ne perampanel muchirwere cheParkinson. Imwe ongororo ingave yakakosha nekudzidza kwembeva uku.

Imwe ongororo yekiriniki inogona kuitwa ndeyekutarisa varwere vane chirwere cheParkinson vane hyposmia. Zvidzidzo zvakati wandei zvakamboitwa kare zvakaratidza kuti varwere vane chirwere cheParkinson vane hyposmia vane mukana wakakura wekuva nedementia zvichienzaniswa nevarwere vane chirwere cheParkinson vasina hyposmia.

Tiri kufunga nezvekuedzwa kwekiriniki kwekushanda kweperampanel pakurwisa dementia muvarwere vane chirwere cheParkinson vane hyposmia.

[00:08:12] Prof. Tiago Outeiro:
Zvakanaka. Saka iboka revanhu iro ringave rine musoro wenyaya yacho. Saka tasvika kumagumo, saka ndinoda kukubvunzai kuti, pane chimwe chinhu chamunoda kutaura nezvekudzidza kwenyu here? Pane chatingave tisina kutaura nezvazvo here? Pane chinhu chakakosha chamunoda kutaura.

[00:08:27] Dr. Norihito Uemura:
Chandinoda kusimbisa ndechekuti chidzidzo ichi hachina kungogumira pamushonga mumwe chete. Chidzidzo ichi chakaratidza kuti tinogona kuongorora mhedzisiro yekurapa kunochinja chirwere pakurwisa kupararira kwealpha-synuclein mumamodheru embeva.

Nechirongwa ichi, tinogona kuongorora mimwe mishonga inogona kushandiswa kuti tione kushanda kwayo pakurwisa kupararira kwealpha-synuclein kubva mumuti we synaptic. Chinangwa chacho chichava chakanaka, uye ndinotarisira kuti mushonga uyu unogadzirisa dambudziko iri uchavapo pazvirwere zvemuviri zveLewy.

[00:09:06] Prof. Tiago Outeiro:
Ehe. Maita basa. Ipfungwa yakanaka kwazvo nekuti makagadzira modhi inogona kubatsira zvikuru pakuedza mamwe marudzi emamorekuru. Saka ndinofunga kuti iyi ishoko rakakoshawo kubva muongororo yenyu. Ehe, munoshuma nezve perampanel, asi nemodhi yamunayo, pamwe mimwe mishonga inogona kuyedzwa, uye izvi zvinogona kuratidzwa kuti zvakakosha.

Saka ndatenda zvikuru. Zvaifadza kutaura nemi uye kudzidza nezvezvamakawana. Ndatenda nenguva yenyu.

[00:09:33] Dr. Norihito Uemura:
Zvinofadza kutaura nemi. Ndatenda zvikuru

[00:09:36] Prof. Tiago Outeiro:
Mazvita. Saka tichangobva kubvunzurudza Dr. Uemura vekuKyoto University neOsaka Metropolitan University muJapan nezvebhuku ravo ravachangobva kuburitsa muMovement Disorders. Saka tinotenda mese nekuteerera uye kubatana nesu mumapodcasts edu ari kuuya.