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Inkasta oo ay naadir tahay, guud ahaan dhacdooyinka kaydinta lysosomal waa qiyaastii 1 ka mid ah 5,000 ee dhallaanka nool. Intaa waxaa dheer, ku dhawaad ​​​​70 ka mid ah cilladaha kaydinta lysosomal ee la yaqaan, 70% waxay saameeyaan habka dhexe ee neerfayaasha. Cilladahan hal-abuurka ah waxay keenaan cillad la'aan lysosomal, taasoo keentay xasillooni-darro dheef-shiid kiimikaad ah, hab-dhisidda borotiinka bartilmaameedka naasleyda ee rapamycin (mTOR, kaas oo sida caadiga ah joojiya caabuqa), autophagy naafo ah, iyo dhimashada unugyada dareemayaasha. Dhowr daawayn oo lagu beegsanayo hababka pathologic ee hoose ee cudurka kaydinta lysosomal ayaa la ansixiyay ama ay ku jiraan horumarinta, oo ay ku jiraan daaweynta beddelka enzyme, daaweynta dhimista substrate, therapy chaperone molecular, daaweynta hidda-socodka, tafatirka hidda-socodka, iyo daaweynta neuroprotective

Cudurka Niemann-pick nooca C waa khalkhalka kolestaroolka gacanta ee kaydinta lysosomal ee uu keeno isbeddellada biilelic ee NPC1 (95%) ama NPC2 (5%). Calaamadaha nooca C ee cudurka Niemann-Pick waxaa ka mid ah si degdeg ah, hoos u dhaca neerfayaasha dilaaga ah ee dhallaanka, halka dhallinta dambe, dhallinta, iyo foomamka bilawga qaangaarka ay ka mid yihiin splenomegaly, dhunkashada supranuclear paralysis iyo cerebellar ataxia, dysarticulationia, iyo waallida sii socota.

Caddadkan joornaalka, Bremova-Ertl et al waxay ka warbixiyeen natiijooyinka laba-indho-indho-indho-indho-labo-labo-labo-koontarool, tijaabo-is-dhaafsi. Tijaabooyinku waxay adeegsadeen wakiilka neuroprotective ee suurtogalka ah, analoogga amino acid N-acetyl-L-leucine (NALL), si loo daaweeyo Niemann-Pick nooca C. Waxay qoreen 60 qaangaar ah oo qaangaar ah iyo bukaannada qaangaarka ah, natiijooyinkuna waxay muujiyeen horumar weyn oo ku yimid wadarta guud ee dhibcaha (dhamaadka koowaad) ee Qiimaynta Ataxia iyo Qiimaynta Qiimaynta.

Tijaabooyinka kiliinikada ee N-acetyl-DL-leucine (Tanganil), jinsiyadda NALL iyo n-acetyl-D-leucine, waxay u muuqdaan inay si weyn u wadaan khibrad: habka ficilka si cad looma caddayn. N-acetyl-dl-leucine ayaa loo oggolaaday daawaynta vertigo ba'an tan iyo 1950-meeyadii; Moodooyinka xayawaanku waxay soo jeedinayaan in daawadu ay shaqeyso iyada oo dib-u-habayn ku samaynaysa xad-dhaafka iyo depolarization neurons vestibular medial. Ka dib, Strup et al. ayaa sheegay natiijooyinka daraasad gaaban oo ay ku arkeen hagaajinta calaamadaha 13 bukaan oo qaba ataxia cerebellar cerebellar ataxia ee kala duwan, natiijooyinka dib u soo celiyay xiisaha daawada mar kale.

Habka ay n-acetyl-DL-leucine u wanaajiso shaqada neerfaha weli ma cadda, laakiin natiijooyinka labada nooc ee jiirka, mid ka mid ah cudurka Niemann-Pick nooca C iyo kan kale ee GM2 ganglioside kaydinta xanuunka Variant O (Cudurka Sandhoff), cudur kale oo neurodegenerative lysosomal, ayaa kiciyay dareenka in loo leexdo NALL. Gaar ahaan, badbaadada Npc1-/- jiirarka lagu daweeyay n-acetyl-DL-leucine ama NALL (L-enantiomers) ayaa wanaajiyay, halka badbaadada jiirarka lagu daweeyay n-acetyl-D-leucine (D-enantiomers) aysan samayn, taasoo soo jeedinaysa in NALL ay tahay qaabka firfircoon ee daawada. Daraasad la mid ah oo ku saabsan GM2 ganglioside kaydinta kala duwanaanshaha xanuunka O (Hexb-/-), n-acetyl-DL-leucine waxay keentay in yar laakiin korodhka nolosha ee jiirarka.

Si loo sahamiyo habka ficilka ee n-acetyl-DL-leucine, cilmi-baarayaashu waxay baareen dariiqa dheef-shiid kiimikaadka ee leucine iyaga oo cabbiraya dheef-shiid kiimikaad ee unugyada cerebellar ee xayawaanka mutant. Qaabka O ee kala duwanaanshiyaha kaydinta ganglioside ee GM2, n-acetyl-DL-leucine waxay caadi ka dhigtaa gulukooska iyo dheef-shiid kiimikaadka glutamate, waxay kordhisaa autophagy, waxayna kordhisaa heerarka superoxide dismutase (qalab ogsijiin firfircoon). Qaabka C ee cudurka Niemann-Pick, isbeddellada gulukooska iyo dheef-shiid kiimikaadka antioxidant iyo hagaajinta dheef-shiid kiimikaadka tamarta mitochondrial ayaa la arkay. In kasta oo L-leucine uu yahay firfircoone firfircoon oo mTOR ah, ma jirin wax isbeddel ah oo ku yimid heerka ama fosforyaalka mTOR ka dib markii lagu daweeyey n-acetyl-DL-leucine ama kuwa soo kordhiyey ee nooc kasta oo jiirka ah.

Saamaynta neuroprotective ee NALL ayaa lagu arkay moodal jiirka ah oo ka hortagaya kortikal dhaawaca maskaxda. Saamayntan waxaa ka mid ah hoos u dhigista calaamadaha neerfaha, yaraynta dhimashada unugyada kortikal, iyo hagaajinta qulqulka autophagy. Daawaynta NALL ka dib, matoorka iyo hawlaha garashada ee jiirarka dhaawacantay waa la soo celiyay waxaana la dhimay xajmiga dhaawaca.

Jawaabta bararka ee habka dhexe ee neerfayaasha ayaa ah calaamadda inta badan cilladaha kaydinta lysosomal neurodegenerative. Haddii xanuunka neuroinflammation lagu yarayn karo daaweynta NALL, calaamadaha bukaan-socodka ee qaar badan, haddaysan ahayn dhammaan, cilladaha kaydinta lysosomal neurodegenerative ayaa laga yaabaa in la hagaajiyo. Sida daraasaddani muujinayso, NALL waxa kale oo la filayaa in ay is-waafajiyaan daawaynta kale ee cudurka kaydinta lysosomal.

Xanuuno badan oo kaydinta lysosomal ayaa sidoo kale lala xiriiriyaa ataxia cerebellar. Marka loo eego daraasad caalami ah oo ku lug leh carruurta iyo dadka waaweyn ee qaba cilladaha kaydinta ganglioside ee GM2 (Cudurka Tay-Sachs iyo cudurka Sandhoff), ataxia waa la dhimay oo isku-dubbaridka dhaqdhaqaaqa wanaagsan ayaa la hagaajiyay ka dib daaweynta NALL. Si kastaba ha noqotee, mid weyn, mid dhexdhexaad ah, laba-indho la'aan, randomized, placebo-control ayaa muujisay in n-acetyl-DL-leucine aysan ahayn mid caafimaad ahaan waxtar u leh bukaanada isku dhafan (dhaxalka, aan la dhaxlo, iyo kuwa aan la garanayn) cerebellar ataxia. Natiijooyinkani waxay soo jeedinayaan in waxtarka lagu arki karo oo keliya tijaabooyinka ku lug leh bukaannada qaba ataxia cerebellar ee la iska dhaxlo iyo hababka ficilka ee la xiriira oo la falanqeeyay. Intaa waxaa dheer, sababtoo ah NALL waxay yaraynaysaa xanuunka neuroinflammation, taas oo keeni karta dhaawac maskaxeed oo naxdin leh, tijaabooyinka NALL ee daaweynta dhaawaca maskaxda ayaa laga yaabaa in la tixgeliyo.