Kuphononongo olupapashwe kwijenali iScience, iqela libonisa ukuba umsebenzi wokuxhuzula ofihlakeleyo ukhuthaza ukudumba kwengqondo okungaqhelekanga kwiimodeli zempuku ezilinganisa imiba ephambili yesifo i-Alzheimer's. Izazinzulu zibonisa ukuba abadlali abaninzi abaziwayo kwisifo se-Alzheimer bangena kule khonkco inomdla phakathi kwenkqubo ye-nervous kunye ne-immune system, kuquka i-protein tau, ehlala iphosakele kwaye idityaniswe kwiingqondo ezigulayo, kunye ne-TREM2, i-genetic risk factor for the disease.
"Iziphumo zethu zibonisa iindlela zokuthintela kunye nokuguqula izinto ezingaqhelekanga ezinxulumene ne-Alzheimer's kuzo zombini uthungelwano lwengqondo kunye nemisebenzi yomzimba," kusho uLennart Mucke, MD, umlawuli weGladstone Institute of Neurological Disease kunye nombhali ophezulu wophando olutsha. "Olu ngenelelo lunokunciphisa iimpawu zesifo kwaye lunokunceda nokuguqula indlela yesi sifo."
Ukuqhagamshela Umsebenzi we-Epileptic kunye nokudumba kwengqondo
Izazinzulu zisazi okwethutyana ukuba isifo sika-Alzheimer sinxulunyaniswa nokudumba okungapheliyo kwengqondo. Umqhubi wolu kuvuvukala kubonakala kukuqokelela kweeprotheni ze-amyloid ngendlela "yamacwecwe," i-neuropathological markmark yesifo.
Kuphononongo olutsha, abaphandi bachonge umsebenzi wokuxhuzula ongaxhuzuki njengomnye umqhubi obalulekileyo wokudumba kwengqondo okungapheliyo kwimodeli yempuku enxulumene ne-Alzheimer. Olu hlobo lufihlakeleyo lomsebenzi wokuxhuzula lwenzeka kwinani elikhulu labantu abanesifo i-Alzheimer kwaye lunokuba luqikelelo lokuhla ngokukhawuleza kwengqondo kwizigulana.
"Enye indlela lo msebenzi wokuxhuzula onokuthi ukhawulezise ukwehla kwengqondo kukukhuthaza ukudumba kwengqondo," utshilo uMelanie Das, PhD, isazinzulu kwiqela le-Mucke kunye nombhali ophambili wephepha. "Sasinovuyo lokufumana iindlela ezimbini zonyango ezicinezela umsebenzi wokuxhuzula kunye nokudumba kwengqondo."
Kwimodeli yegundane, izazinzulu zithintele zombini izinto ezingaqhelekanga ngokusebenzisa ubunjineli bezofuzo ukuphelisa iprotein tau, ekhuthaza i-neuronal hyperexcitability (ukudubula kwee-neurons ezininzi ngexesha elinye). Baye bakwazi ukuguqula utshintsho kwinethiwekhi ye-neural kunye neeseli zomzimba, ubuncinane ngokuyinxalenye, ngokunyanga iigundane nge-anti-epileptic drug levetiracetam.
Ulingo lwakutsha nje lweklinikhi lwe-levetiracetam oluye lwavela kumsebenzi wangaphambili we-Mucke lubonise izibonelelo zengqondo kwizigulane ezine-Alzheimer's disease kunye ne-subclinical epileptic umsebenzi, kunye ne-tau-downing therapeutics ziphantsi kophuhliso, kunye nokwakhiwa kophando kwilebhu ye-Mucke. Uphononongo olutsha luqinisekisa ukuba olu nyango lunokuthembisa kangakanani na kubantu abakumanqanaba okuqala esifo i-Alzheimer's.
Umsebenzi weNoveli woMngcipheko wemfuza we-Alzheimer onempembelelo
Ukudumba akufani konke; inokuqhuba isifo, njengoko kunjalo kwiimeko ezifana ne-rheumatoid arthritis, okanye inokunceda umzimba uphilise, umzekelo, emva kokusikwa.
"Kubalulekile ukwahlula ukuba isifo se-Alzheimer sibangela ukudumba okubi kakhulu, ukungaphumeleli kokudumba okulungileyo, okanye zombini," utsho uMcke, okwanguJoseph B. Martin onguNjingalwazi oBalulekileyo we-Neuroscience kunye noprofesa we-neurology e-UC San Francisco. "Ukujonga ukusebenza kweeseli ezikrala engqondweni akukuxeleli ngoko nangoko ukuba ukusebenza kulungile okanye kubi, ngoko sigqibe kwelokuba siphande ngakumbi."
U-Mucke kunye noogxa bakhe bafumanisa ukuba, xa benciphisa umsebenzi wokuxhuzula kwingqondo yegundane, enye yezinto ezibangela ukudumba okuchaphazeleka kakhulu yi-TREM2, eveliswa yi-microglia, iiseli zomzimba ezihlala kwingqondo. Abantu abaneemo zemfuza ze-TREM2 banamathuba amabini ukuya kwamane okuba baphuhle isifo se-Alzheimer kunabantu abane-TREM2 eqhelekileyo, kodwa izazinzulu zisazama ukucacisa iindima ezithe ngqo ezidlalwa yile molekyuli kwimpilo nakwizifo.
Izazinzulu zaqala zabonisa ukuba i-TREM2 yonyuswa ebuchotsheni beempuku kunye namacwecwe e-amyloid, kodwa yancitshiswa emva kokucinezelwa komsebenzi wabo wokuxhuzula. Ukufumanisa ukuba kutheni, baye bavavanya ukuba ingaba i-TREM2 iyakuchaphazela ukubakho kweempuku kwiidosi eziphantsi zechiza elinokubangela ukuxhuzula. Iimpuku ezinamaqondo ancitshisiweyo e-TREM2 zibonise umsebenzi wokuxhuzula ngakumbi ekuphenduleni eli chiza kuneempuku ezinamazinga aqhelekileyo e-TREM2, ebonisa ukuba i-TREM2 inceda i-microglia icinezele imisebenzi engaqhelekanga ye-neuronal.
"Le ndima ye-TREM2 ibingalindelekanga kwaye icebisa ukuba amanqanaba okwanda kwe-TREM2 engqondweni anokuthi abe nenjongo eluncedo," utshilo uDas. "I-TREM2 ifundwe ngokunxulumene neempawu ze-pathological ze-Alzheimer's disease ezifana namacwecwe kunye ne-tangles. Apha, sifumanise ukuba le molekyuli ikwanendima ekulawuleni imisebenzi yenethiwekhi ye-neural.
"Iintlobo zofuzo ze-TREM2 ezonyusa umngcipheko wesifo se-Alzheimer zibonakala ziphazamisa umsebenzi wayo," wongeza uMcke. "Ukuba i-TREM2 ayisebenzi kakuhle, kunokuba nzima kwiiseli zomzimba ukucinezela i-neuronal hyperexcitability, enokuthi ibe negalelo kuphuhliso lwesifo se-Alzheimer kunye nokukhawulezisa ukuncipha kwengqondo."
Iinkampani ezininzi zamachiza ziphuhlisa amajoni omzimba kunye nezinye iikhompawundi zokuphucula umsebenzi we-TREM2, ngokukodwa ukunyusa ukususwa kwamacwecwe e-amyloid. NgokukaMucke, unyango olunjalo lunokunceda ukucinezela umsebenzi ongaqhelekanga wothungelwano kwisifo sika-Alzheimer kunye neemeko ezinxulumeneyo.
INTO ONOKUYITHATHA KWELI NQAKU:
- The scientists show that multiple known players in Alzheimer’s disease fit into this intriguing link between the nervous system and the immune system, including the protein tau, often misfolded and aggregated in diseased brains, and TREM2, a genetic risk factor for the disease.
- This subtle type of epileptic activity also occurs in a substantial proportion of people with Alzheimer’s disease and can be a predictor of faster cognitive decline in the patients.
- “Looking at the activation of inflammatory cells in the brain doesn’t immediately tell you whether the activation is good or bad, so we decided to investigate further.
