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Ulalo Watsopano Wapezeka Pakati pa Alzheimer's ndi Immune Cell Dysfunctions

Written by mkonzi

Kuphunzira zovuta zomwe zimayambitsa matenda a Alzheimer's, ndi momwe mungachiritsire ndi kupewa matendawa, kuli ngati kuthetsa zojambulajambula zambiri, ndi asayansi aliyense akulimbana ndi gawo laling'ono, osadziŵa momwe lingagwirizane ndi chithunzi chachikulu. Tsopano, ofufuza a Gladstone Institutes atsimikiza momwe magawo angapo azithunzi omwe anali osalumikizidwa amalumikizana.

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Pakafukufuku wofalitsidwa mu nyuzipepala ya iScience, gululi likuwonetsa kuti zochitika zobisika za khunyu zimalimbikitsa kutupa kwaubongo kwamtundu wa mbewa zomwe zimatengera mbali zazikulu za matenda a Alzheimer's. Asayansi akuwonetsa kuti osewera ambiri odziwika mu matenda a Alzheimer's amalowa mu ulalo wochititsa chidwiwu pakati pa dongosolo lamanjenje ndi chitetezo chamthupi, kuphatikiza mapuloteni a tau, omwe nthawi zambiri amasokonekera ndikuphatikizidwa muubongo wodwala, ndi TREM2, chomwe chimayambitsa matenda.

"Zomwe tapeza zikuwonetsa njira zopewera ndikusintha zovuta zokhudzana ndi Alzheimer's mu maukonde onse aubongo komanso magwiridwe antchito a chitetezo chamthupi," akutero Lennart Mucke, MD, mkulu wa Gladstone Institute of Neurological Disease komanso wolemba wamkulu wa kafukufuku watsopano. "Zochita izi zitha kuchepetsa zizindikiro za matenda komanso zingathandize kusintha momwe matendawa akuyendera."

Kugwirizanitsa Ntchito Zakhunyu ndi Kutupa Kwaubongo

Asayansi adziwa kwakanthawi kuti matenda a Alzheimer's amalumikizidwa ndi kutupa kosatha muubongo. Woyendetsa wa kutupa uku akuwoneka ngati kudziunjikira kwa mapuloteni amyloid mu mawonekedwe a "plaques," chizindikiro cha matenda a neuropathological.

Mu kafukufuku watsopanoyu, ofufuzawo adazindikira zochitika za khunyu zomwe sizimagwedezeka ngati dalaivala wina wofunikira kwambiri wa kutupa kwaubongo mumtundu wa mbewa wokhudzana ndi Alzheimer's. Mtundu wobisika wamtunduwu wa khunyu umapezekanso mwa anthu ambiri omwe ali ndi matenda a Alzheimer's ndipo amatha kuwonetsa kuchepa kwachidziwitso kwa odwala.

"Njira imodzi ya khunyu iyi ingathandizire kuchepa kwa chidziwitso ndikulimbikitsa kutupa muubongo," akutero Melanie Das, PhD, wasayansi m'gulu la Mucke komanso wolemba wamkulu wa pepalalo. "Tinali okondwa kupeza njira ziwiri zochiritsira zomwe zimachepetsa khunyu komanso kutupa muubongo."

Muchitsanzo cha mbewa, asayansi adaletsa zolakwika zonsezo pogwiritsa ntchito genetic engineering kuti athetse puloteni ya tau, yomwe imalimbikitsa neuronal hyperexcitability (kuwombera kwa ma neuroni ambiri nthawi imodzi). Anathanso kusintha kusintha kwa neural network ndi maselo a chitetezo chamthupi, makamaka mwa zina, pochiza mbewa ndi mankhwala oletsa khunyu levetiracetam.

Mayesero aposachedwa azachipatala a levetiracetam omwe adatuluka mu ntchito yapitayi ya Mucke adawulula zopindulitsa zachidziwitso kwa odwala omwe ali ndi matenda a Alzheimer's ndi subclinical khunyu, komanso chithandizo chotsitsa tau-kutsitsa chikukulirakulira, ndikumanganso kafukufuku mu labotale ya Mucke. Kafukufuku watsopanoyu akutsimikiziranso momwe chithandizochi chingakhalire chodalirika kwa anthu omwe ali ndi matenda a Alzheimer's.

Ntchito Yatsopano Yamtundu Wowopsa wa Alzheimer's Risk Gene

Kutupa sikuli kofanana; imatha kuyendetsa matenda, monga momwe zimakhalira ngati nyamakazi ya nyamakazi, kapena ingathandize thupi kuchira, mwachitsanzo, pambuyo podulidwa.

"Ndikofunikira kusiyanitsa ngati matenda a Alzheimer's amachititsa kutupa koipa kwambiri, kulephera kwa kutupa kwabwino, kapena zonsezi," anatero Mucke, yemwenso ndi Joseph B. Martin Pulofesa Wodziwika wa Neuroscience ndi pulofesa wa sayansi ya ubongo ku UC San Francisco. "Tikayang'ana kuyambika kwa ma cell otupa muubongo sikukuuzani nthawi yomweyo ngati kuyambitsako kuli kwabwino kapena koyipa, chifukwa chake tidaganiza zofufuza zambiri."

Mucke ndi anzake adapeza kuti, pamene adachepetsa zochitika za khunyu mu ubongo wa mbewa, chimodzi mwazinthu zotupa zomwe zimakhudzidwa kwambiri ndi TREM2, yomwe imapangidwa ndi microglia, maselo oteteza chitetezo mu ubongo. Anthu omwe ali ndi mitundu yosiyanasiyana ya TREM2 ali ndi mwayi wokhala ndi matenda a Alzheimer's kuwirikiza kanayi kuposa anthu omwe ali ndi TREM2 yabwinobwino, koma asayansi akuyesabe kumasulira bwino ntchito zomwe molekyuluyi imachita paumoyo ndi matenda.

Asayansi adawonetsa koyamba kuti TREM2 idawonjezeredwa muubongo wa mbewa wokhala ndi zolembera za amyloid, koma idachepetsedwa pambuyo poletsa ntchito yawo ya khunyu. Kuti adziwe chifukwa chake, adafufuza ngati TREM2 imakhudza kutengeka kwa mbewa ku mlingo wochepa wa mankhwala omwe angayambitse khunyu. Makoswe okhala ndi milingo yocheperako ya TREM2 adawonetsa zochitika zambiri za khunyu poyankha mankhwalawa kuposa mbewa zokhala ndi milingo ya TREM2 yabwinobwino, kutanthauza kuti TREM2 imathandiza ma microglia kupondereza zochitika za neuronal.

"Ntchito ya TREM2 iyi inali yosayembekezereka ndipo ikuwonetsa kuti kuchuluka kwa TREM2 muubongo kumatha kukhala kopindulitsa," akutero Das. "TREM2 idaphunziridwa makamaka pokhudzana ndi zizindikiro za matenda a Alzheimer's monga zolembera ndi ma tangles. Apa, tapeza kuti molekyulu iyi ilinso ndi gawo pakuwongolera magwiridwe antchito a neural network. ”

"Mamitundu amtundu wa TREM2 omwe amawonjezera chiopsezo cha matenda a Alzheimer's akuwoneka kuti amawononga ntchito yake," akuwonjezera Mucke. "Ngati TREM2 siyikuyenda bwino, zitha kukhala zovuta kuti ma cell a chitetezo chamthupi achepetse kukhumudwa kwa neuronal, zomwe zimathandizira kukulitsa matenda a Alzheimer's ndikufulumizitsa kuchepa kwa chidziwitso."

Makampani angapo opanga mankhwala akupanga ma antibodies ndi mankhwala ena kuti apititse patsogolo ntchito ya TREM2, makamaka kuti apititse patsogolo kuchotsedwa kwa zolembera za amyloid. Malinga ndi Mucke, chithandizo choterocho chingathandizenso kupondereza zochitika zapaintaneti mu matenda a Alzheimer's ndi zina zofananira.

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mkonzi

Mkonzi wamkulu ndi Linda Hohnholz.

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