نتایج جستجو برای: secretase

تعداد نتایج: 3434  

2013
Bart De Strooper

Over the last decade important progress has been made towards the understanding of the molecular pathobiology of Alzheimer’s Disease. One of the major breakthroughs was the identification of presenilin and its crucial role in the gamma-Secretase processing of APP and Notch. Ever since, it has been a major aim to block gamma-Secretase in a safe way. Recent results of trials, in particular the se...

2010
Yasuhiro Teranishi Ji-Yeun Hur Hedvig Welander Jenny Frånberg Mikio Aoki Bengt Winblad Susanne Frykman Lars O Tjernberg

γ-Secretase is a transmembrane protease complex responsible for the processing of a multitude of type 1 transmembrane proteins, including amyloid precursor protein (APP) and Notch. A functional complex is dependent on the assembly of four proteins: presenilin (PS), nicastrin, Aph-1 and Pen-2. Little is known about how the substrates are selected by γ-secretase, but it has been suggested that γ-...

Journal: :Current Biology 2002
Eric C Lai

Presenilin is thought to be the proteolytic component of gamma-secretase, responsible for the intramembranous cleavage of substrates that include the activated Notch receptor. Recent studies have identified the novel protein Nicastrin as another essential component of the Presenilin/gamma-secretase complex.

2013
Marcus O. W. Grimm Viola J. Haupenthal Tatjana L. Rothhaar Valerie C. Zimmer Sven Grösgen Benjamin Hundsdörfer Johannes Lehmann Heike S. Grimm Tobias Hartmann

Alzheimer's disease (AD) is characterized by extracellular accumulation of amyloid-β peptide (Aβ), generated by proteolytic processing of the amyloid precursor protein (APP) by β- and γ-secretase. Aβ generation is inhibited when the initial ectodomain shedding is caused by α-secretase, cleaving APP within the Aβ domain. Therefore, an increase in α-secretase activity is an attractive therapeutic...

2017
Zhaoyi Feng Wandong Xu Chenguang Zhang Mengran Liu Hongwu Wen

Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of γ-secretase and the mechanism of how γ-secretase inhibitor works on cancer cell. Here, we show that Jagge...

2016
Sophia Schedin-Weiss Ina Caesar Bengt Winblad Hans Blom Lars O. Tjernberg

The transmembrane protein assembly γ-secretase is a key protease in regulated intramembrane processing (RIP) of around 100 type-1 transmembrane proteins. Importantly, it has a pathological role in Alzheimer disease (AD) as it generates the neurotoxic amyloid β-peptide from the amyloid precursor protein (APP). Studies on γ-secretase location are therefore crucial both from a biological and a the...

2015
Maria Szaruga Sarah Veugelen Manasi Benurwar Sam Lismont Diego Sepulveda-Falla Alberto Lleo Natalie S. Ryan Tammaryn Lashley Nick C. Fox Shigeo Murayama Harrie Gijsen Bart De Strooper Lucía Chávez-Gutiérrez

Presenilin (PSEN) pathogenic mutations cause familial Alzheimer's disease (AD [FAD]) in an autosomal-dominant manner. The extent to which the healthy and diseased alleles influence each other to cause neurodegeneration remains unclear. In this study, we assessed γ-secretase activity in brain samples from 15 nondemented subjects, 22 FAD patients harboring nine different mutations in PSEN1, and 1...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2015
Shangyu Dang Shenjie Wu Jiawei Wang Hongbo Li Min Huang Wei He Yue-Ming Li Catherine C L Wong Yigong Shi

Aberrant cleavage of amyloid precursor protein (APP) by γ-secretase contributes to the development of Alzheimer's disease. More than 200 disease-derived mutations have been identified in presenilin (the catalytic subunit of γ-secretase), making modulation of γ-secretase activity a potentially attractive therapeutic opportunity. Unfortunately, the technical challenges in dealing with intact γ-se...

Journal: :PLoS ONE 2009
Lisa Placanica Lei Zhu Yue-Ming Li

Alzheimer disease (AD) is an age-related disorder. Aging and female gender are two important risk factors associated with sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is unclear. It is well known that genetic mutations in gamma-secretase result in rare forms of early onset AD due to the aberrant production of Abeta42 peptides, which...

2016
Tian Tian Dong Bai Wen Li Guo-Wei Huang Huan Liu

Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this r...

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