1篇
您的检索式：作者名="Andrew S.Neish"
|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Initiation of Parkinson’s disease from gut to brain byδ-secretase显示文摘Lewy pathology,composed ofα-Synuclein(α-Syn)inclusions,a hallmark of Parkinson’s disease(PD),progressively spreads from the enteric nervous system(ENS)to the central nervous system(CNS).However,it remains unclear how this process is regulated at a molecular level.Here we show thatδ-secretase(asparagine endopeptidase,AEP)cleaves bothα-Syn at N103 and Tau at N368,and mediates their fibrillization and retrograde propagation from the gut to the brain,triggering nigra dopaminergic neuronal loss associated with Lewy bodies and motor dysfunction.α-Syn N103 and Tau N368 robustly interact with each other and are highly elevated in PD patients’gut and brain.Chronic oral administration of the neurotoxin rotenone induces AEP activation andα-Syn N103/Tau N368 complex formation in the gut,eliciting constipation and dopaminergic neuronal death in an AEP-dependent manner.Preformed fibrils(PFFs)ofα-Syn N103/Tau N368 are more neurotoxic and compact,and aggregate more quickly along the vagus nerve than their FL/FL counterparts or the individual fragments’fibrils.Colonic injection of PFFs induces PD pathologies,motor dysfunctions,and cognitive impairments.Thus,δ-secretase plays a crucial role in initiating PD pathology progression from the ENS to the CNS. | Eun Hee Ahn Seong Su Kang Xia Liu Guiqin Chen Zhentao Zhang Bindu Chandrasekharan Ashfaqul M.Alam Andrew S.Neish Xuebing Cao Keqiang Ye | 2020 | Cell Research2020，30，1： | 9 |
您所在的机构暂未开通此部分的功能，请联系管理员