Results 31 to 40 of about 38,664 (219)

Substrate‐Selective Inhibition of the SARS‐CoV‐2 Papain‐Like Protease: Inhibition of Hydrolysis of Human Over Viral Substrates

Chemistry – A European Journal, EarlyView.
The SARS‐CoV‐2 papain‐like protease (PLpro) is a medicinal chemistry target. Here we report mass spectrometry assays employing oligopeptide substrates based on the sequences of the viral polyproteins 1a/1ab and on an ISG15‐modified human protein, which enabled the identification of substrate‐selective PLpro inhibitors.
Sakshi Sharma, Peter A. C. Wing, Wojtek Treyde, Shyam Basak, Simeon D. Draganov, Taylah Andrews‐Clark, Eidarus Salah, Petra Lukacik, Claire Strain‐Damerell, Adán Pinto‐Fernández, Martin A. Walsh, Fernanda Duarte, Christopher J. Schofield, Lennart Brewitz   +13 more
wiley   +1 more source

Caveolin‐1 inhibition mediates the opposing effects of alcohol on γ‐secretase activity in arterial endothelial and smooth muscle cells

Physiological Reports, 2023
Notch is important to vessel homeostasis. We investigated the mechanistic role of caveolin‐1 (Cav‐1) in mediating the effects of alcohol (Ethanol/EtOH) on the γ‐secretase proteolytic activity necessary for Notch signaling in vascular cells.
Naresh K. Rajendran, Weimin Liu, Paul A. Cahill, Eileen M. Redmond   +3 more
doaj   +1 more source

Intravenous Lipopolysaccharide Challenge in Healthy Participants Reveals Pharmacodynamic Markers in Blood and Bone Marrow for Early‐Phase Oncology Drug Development

Clinical Pharmacology &Therapeutics, EarlyView.
Demonstrating pharmacological effects in early‐phase oncology clinical trials remains challenging, largely due to the lack of robust pharmacodynamic markers. Lipopolysaccharide (LPS) is used as an immune challenge agent in healthy participants to study drugs for autoimmune conditions.
Igor Radanović, Ingrid Tomljanović, Wieke H. Grievink, Diana R. Pereira, Michelle Osse, Peter van Balen, Maria J. Juachon, Marieke L. de Kam, Lisa Pagan, Manon A.A. Jansen, Matthijs Moerland, Jacobus J. Bosch   +11 more
wiley   +1 more source

Recording γ-secretase activity in living mouse brains

eLife
γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell ...
Steven S Hou, Yuya Ikegawa, Yeseo Kwon, Natalia Wieckiewicz, Mei CQ Houser, Brianna Lundin, Brian J Bacskai, Oksana Berezovska, Masato Maesako   +8 more
doaj   +1 more source

Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism

Neurobiology of Disease, 2005
In Alzheimer's disease, the complex catabolism of amyloid precursor protein (APP) leads to the production of amyloid-beta (Abeta) peptide, the major component of amyloid deposits.
Valérie Vingtdeux, Malika Hamdane, Marie Gompel, Séverine Bégard, Hervé Drobecq, Antoine Ghestem, Marie-Eve Grosjean, Vesna Kostanjevecki, Pierre Grognet, Eugeen Vanmechelen, Luc Buée, André Delacourte, Nicolas Sergeant   +12 more
doaj   +1 more source

AKT, ATR, and Notch Inhibitors Radiosensitize a Preclinical Model of Adenoid Cystic Carcinoma

Head &Neck, EarlyView.
ABSTRACT Background Adenoid Cystic Carcinoma (ACC) is a rare and lethal type of head and neck cancer. Standard therapy involves surgery followed by radiation therapy. The majority of ACC has MYB overexpression and MYB‐NFIB gene fusions, while Notch mutations are associated with aggressive behavior.
Shivani Thoidingjam, Sushmitha Sriramulu, Asya Haider Muratoglu, Stephen Brown, Oudai Hassan, Benjamin Movsas, Haythem Ali, Steven Chang, Patrick Ha, Farzan Siddiqui, Shyam Nyati   +10 more
wiley   +1 more source

Secretase promotes AD progression: simultaneously cleave Notch and APP

Frontiers in Aging Neuroscience
Alzheimer’s disease (AD) involves complex pathological mechanisms. Secretases include membrane protein extracellular structural domain proteases and intramembrane proteases that cleave the topology to type I or type II.
Ke-Fan Yang, Jing-Yi Zhang, Mei Feng, Kuo Yao, Yue-Yang Liu, Ming-Sheng Zhou, Hui Jia, Hui Jia   +7 more
doaj   +1 more source

The resveratrol trimer miyabenol C inhibits β-secretase activity and β-amyloid generation.

PLoS ONE, 2015
Accumulation and deposition of amyloid-β peptide (Aβ) in the brain is a primary cause of the pathogenesis of Alzheimer's disease (AD). Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages first by β-secretase and then by γ ...
Jin Hu, Ting Lin, Yuehong Gao, Junyue Xu, Chao Jiang, Guanghui Wang, Guojun Bu, Huaxi Xu, Haifeng Chen, Yun-wu Zhang   +9 more
doaj   +1 more source

Somatic cell reprogramming for Parkinson's disease treatment

Ibrain, Volume 11, Issue 1, Page 59-73, Spring 2025.
The fundamental purpose of cell reprogramming to treat Parkinson's disease is to generate dopaminergic neurons (DAN) and do transplantation. There are two ways to accomplish this. One method is to induce cells into induced DA neurons (iDAN) directly or to induce cells into induced pluripotent stem cells and ultimately into iDAN in vitro. Another option
Xiaozhuo Li, Kevin Fang, Fengping Wang
wiley   +1 more source

Cellular basis of Alzheimer′s disease

Annals of Indian Academy of Neurology, 2010
Alzheimer′s disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is ...
Bali Jitin, Halima Saoussen, Felmy Boas, Goodger Zoe, Zurbriggen Sebastian, Rajendran Lawrence   +5 more
doaj