Results 61 to 70 of about 29,069 (201)

Endoproteolysis of the ER Stress Transducer ATF6 in the Presence of Functionally Inactive Presenilins

Neurobiology of Disease, 2001
Presenilin (PS) proteins facilitate endoproteolysis of selected type I transmembrane proteins such as the Alzheimer's disease (AD) associated β-Amyloid precursor protein (βAPP) and Notch.
Harald Steiner, Edith Winkler, Mark S. Shearman, Ron Prywes, Christian Haass   +4 more
doaj   +1 more source

Modulation of γ-secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer's disease. [PDF]

PLoS ONE, 2012
BACKGROUND: We describe molecular processes that can facilitate pathogenesis of Alzheimer's disease (AD) by analyzing the catalytic cycle of a membrane-imbedded protease γ-secretase, from the initial interaction with its C99 substrate to the final ...
Zeljko M Svedružić, Katarina Popović, Ivana Smoljan, Vesna Sendula-Jengić   +3 more
doaj   +1 more source

Pathogenesis of Age‐Related Hearing Loss and Therapeutic Strategies

Sensory Neuroscience, EarlyView.
ABSTRACT Age‐related hearing loss (ARHL) is a degenerative disorder of the auditory system, characterized by bilateral symmetrical sensorineural hearing loss that occurs with aging. As a highly prevalent age‐related condition worldwide, ARHL significantly impairs both the quality of life and mental health of the elderly.
Yu Xiao, Jiaxin Liu, Xiaohan Zhang, Miao Chang, Cheng Cheng, Yunhao Wu, Xiaolong Fu   +6 more
wiley   +1 more source

Brain Pericytes and Wnt/β‐Catenin Signaling Induce Functional Blood–Brain Barrier Phenotype in Human iPSC‐Derived Model

Small Methods, EarlyView.
This study shows that human iPSC‐derived endothelial cells acquire a functional blood–brain barrier phenotype when co‐cultured with brain pericytes and stimulated with CHIR‐99021, a Wnt/β‐catenin activator. This model recapitulates key barrier properties, inflammatory responses, and transcriptomic features of the native human BBB, offering new ...
Henrique Nogueira Pinto, Nine R. Kok, Philipp C. Hauger, Manon Karsten‐van Diepen, Michael de Kok, Nanne J. Paauw, Susanne M. A. van der Pol, Joline P. Nugteren‐Boogaard, Peter L. Hordijk, Stephanie D. Beekhuis‐Hoekstra, Susan Gibbs, Nienke M. de Wit, Helga E. de Vries   +12 more
wiley   +1 more source

SUSD2 Promotes Metastasis and Primary Tumor Growth in Pancreatic Cancer Cells via Integrin–FAK Signaling Activation

Cancer Science, EarlyView.
This study investigates the role of Sushi domain‐containing 2 (SUSD2) in pancreatic ductal adenocarcinoma (PDAC) and demonstrates that SUSD2 enhances both metastasis and primary tumor growth by promoting integrin β1–FAK signaling. SUSD2 interacts with integrin β1, enhancing adhesion to extracellular matrix (ECM) components such as collagen 1 and ...
Junjiro Yoshida, Tomokazu Ohishi, Isao Momose, Shun‐ichi Ohba, Kyohei Kurosawa, Akiko Harakawa, Hiroyuki Inoue, Minori Senoo, Daisuke Tatsuda, Hikaru Abe, Atsushi Masamune, Manabu Kawada   +11 more
wiley   +1 more source

Cholesterol retention in Alzheimer's brain is responsible for high β- and γ-secretase activities and Aβ production

Neurobiology of Disease, 2008
Alzheimer's disease (AD) is characterized by overproduction of Aβ derived from APP cleavage via β- and γ-secretase pathway. Recent evidence has linked altered cholesterol metabolism to AD pathogenesis. In this study, we show that AD brain had significant
Huaqi Xiong, Debbie Callaghan, Aimee Jones, Douglas G. Walker, Lih-Fen Lue, Thomas G. Beach, Lucia I. Sue, John Woulfe, Huaxi Xu, Danica B. Stanimirovic, Wandong Zhang   +10 more
doaj   +1 more source

Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets

Cell Proliferation, EarlyView.
This review elucidates the intricate cellular signalling networks involved in high‐altitude pulmonary hypertension (HAPH), integrating canonical pathways like HIF, MAPK and BMP with emerging targets such as Wnt/β‐catenin, Notch, Hippo‐YAP and IL‐6. It highlights potential therapeutic strategies targeting these pathways to mitigate vascular remodelling ...
Sheng Ding, Ju Chen, Zhaoyang Li, Yang Yu, Weijie Wang, Yan Liao, Jin Yang, Dianxiang Lu, Yujiang Fan   +8 more
wiley   +1 more source

Conserved “PAL” sequence in presenilins is essential for γ-secretase activity, but not required for formation or stabilization of γ-secretase complexes

Neurobiology of Disease, 2004
Generation of Aβ from the β-amyloid precursor protein (APP) requires a series of proteolytic processes, including an intramembranous cleavage catalyzed by an aspartyl protease, γ-secretase.
Jun Wang, Anne L Brunkan, Silva Hecimovic, Emily Walker, Alison Goate   +4 more
doaj   +1 more source

Dimerization‐dependent NOTCH receptor transactivation unveils a class of highly selective NOTCH signalling inhibitors

The FEBS Journal, EarlyView.
NOTCH signalling is indispensable for tissue homeostasis and, consequently, corruption of its normal function promotes numerous diseases, including cancer. However, the development of targeted therapies has been hampered by inefficacy and overt toxicity. Here, we show that NOTCH receptor dimerization is necessary for receptor transactivation, which has
Xinxin Liu, Haijiang Wang, Gunja Mishra, Lin‐Ting Wu, Chao Li, Maarten van Dinther, Jin Liu, Manuel A.F.V. Gonçalves, Peter ten Dijke, David A. Baker   +9 more
wiley   +1 more source

Targeting the Notch receptor dimerization domain to inhibit Notch signalling—A new avenue of therapeutics

The FEBS Journal, EarlyView.
Notch signalling is an evolutionarily conserved signalling pathway that directs cell growth and differentiation across multiple tissue types, and its regulation must be controlled across the lifespan. Aberrant Notch signalling due to genetic mutations that occur within the negative regulatory region of the Notch 1 gene is linked to the development of ...
Gerard F Hoyne
wiley   +1 more source