Results 51 to 60 of about 3,289 (188)

The Large Ectodomain of APP Prevents APP from being Directly Cleaved by γ-Secretase

Frontiers in Bioscience-Landmark
Background: Alzheimer’s disease (AD) is characterized by the deposition of amyloid-β peptide (Aβ) in the brain. Aβ is produced by sequential β- and γ-secretase cleavages of amyloid precursor protein (APP).
Yuan Li, Hejie Li, Wenping Liang, Yu Li, Zhe Wang   +4 more
doaj   +1 more source

γ-Secretase Studied by Atomistic Molecular Dynamics Simulations: Global Dynamics, Enzyme Activation, Water Distribution and Lipid Binding

Frontiers in Chemistry, 2019
γ-secretase, an intramembrane-cleaving aspartyl protease is involved in the cleavage of a large number of intramembrane proteins. The most prominent substrate is the amyloid precursor protein, whose proteolytic processing leads to the production of ...
Manuel Hitzenberger, Martin Zacharias
doaj   +1 more source

Loss of Notch signaling in skeletal stem cells enhances bone formation with aging

Bone Research, 2023
Skeletal stem and progenitor cells (SSPCs) perform bone maintenance and repair. With age, they produce fewer osteoblasts and more adipocytes leading to a loss of skeletal integrity.
Lindsey H. Remark, Kevin Leclerc, Malissa Ramsukh, Ziyan Lin, Sooyeon Lee, Backialakshmi Dharmalingam, Lauren Gillinov, Vasudev V. Nayak, Paulo El Parente, Margaux Sambon, Pablo J. Atria, Mohamed A. E. Ali, Lukasz Witek, Alesha B. Castillo, Christopher Y, Park, Ralf H. Adams, Aristotelis Tsirigos, Sophie M. Morgani, Philipp Leucht   +18 more
doaj   +1 more source

Microglial Rack1 Deficiency Alleviates Alzheimer's Disease Pathology through Enhancing IGF1‐Mediated Astrocytic Phagocytosis

Advanced Science, Volume 13, Issue 3, 14 January 2026.
Alzheimer's disease (AD) is the most common neurodegenerative disorder. This study demonstrates that microglial Rack1 deficiency decreased Aβ deposition and neuroinflammation and ameliorated cognitive impairments in AD model mice by enhancing IGF1‐mediated astrocytic phagocytosis.
Jingdan Zhang, Yanling He, Pin Yang, Hengchang Zhang, Yueyang Tong, Lingling Jiang, Zehan Li, Meichen Yan, Xiaoheng Li, Qinghu Yang, Jing Yang, Zengqiang Yuan, Jiyan Zhang, Jinbo Cheng   +13 more
wiley   +1 more source

Immature nicastrin stabilizes APH‐1 independent of PEN‐2 and presenilin: identification of nicastrin mutants that selectively interact with APH‐1 [PDF]

Journal of Neurochemistry, 2004
Abstractγ‐Secretase is a high molecular mass aspartyl protease complex composed of presenilin (PS1 or PS2), nicastrin (Nct), anterior pharynx‐defective‐1 (APH‐1) and presenilin enhancer‐2 (PEN‐2). The complex mediates the intramembraneous proteolysis of β‐secretase cleaved β‐amyloid precursor protein (APP) leading to the secretion of the Alzheimer's ...
Keiro, Shirotani, Dieter, Edbauer, Marcus, Kostka, Harald, Steiner, Christian, Haass   +4 more
openaire   +2 more sources

Protein-sphingolipid interactions within cellular membraness⃞

Journal of Lipid Research, 2008
Each intracellular organelle critically depends on maintaining its specific lipid composition that in turn contributes to the biophysical properties of the membrane.
Per Haberkant, Oliver Schmitt, F.-Xabier Contreras, Christoph Thiele, Kentaro Hanada, Hein Sprong, Constanze Reinhard, Felix T. Wieland, Britta Brügger   +8 more
doaj   +1 more source

Expression of Amyloid Precursor Protein, Caveolin-1, Alpha-, Beta-, and Gamma-Secretases in Penumbra Cells after Photothrombotic Stroke and Evaluation of Neuroprotective Effect of Secretase and Caveolin-1 Inhibitors

Biomedicines, 2022
Our studies reveal changes in the expression of the main participants in the processing of amyloid precursor protein (APP) in neurons and astrocytes after photothrombotic stroke (PTS). Here we show the increase in the level of N- and C-terminal fragments
Svetlana Sharifulina, Andrey Khaitin, Valeria Guzenko, Yuliya Kalyuzhnaya, Valentina Dzreyan, Alexandr Logvinov, Natalia Dobaeva, Yan Li, Lei Chen, Bin He, Svetlana Demyanenko   +10 more
doaj   +1 more source

Natural Products Targeting Notch Signaling in Cancer: Mechanistic Insights and Food‐Based Chemoprevention Potential

Food Frontiers, Volume 7, Issue 1, January 2026.
The Notch signaling pathway plays a dual role in cancer, acting as both a tumor promoter and suppressor depending on cellular context. This review highlights how natural products modulate Notch signaling to inhibit tumor initiation, progression, angiogenesis, and cancer stem cell maintenance.
Rabab Fatima, Parteek Prasher, Mousmee Sharma, Dietrich Büsselberg, Gabriela Figueroa‐González, Octavio Daniel Reyes‐Hernández, Edgar Yebrán Villegas‐Vázquez, Hernán Cortés, Gerardo Leyva‐Gómez, Jesús Herrera‐Bravo, Solomon Habtemariam, Javad Sharifi‐Rad, Monica Butnariu, Cristian Berar, Angela Caunii, William C. Cho   +15 more
wiley   +1 more source

Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets

CNS Neuroscience &Therapeutics, Volume 31, Issue 12, December 2025.
The limited clinical efficacy of anti‐Aβ antibodies has challenged the Aβ hypothesis, compelling the integration of key mechanisms—including neuroinflammation, mitochondrial dysfunction, oxidative stress, and post‐translational modifications of Aβ—into a revised model of Alzheimer's disease.
Shamseddin Ahmadi, Shiler Khaledi, Kimia Ahmadi, Kambiz Hassanzadeh   +3 more
wiley   +1 more source

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype [PDF]

Proceedings of the National Academy of Sciences, 2002
Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms.
Gu, Y, Bergeron, C, Mathews, PM, Nixon, RA, Schmidt, SD, Huang, J, Erdebil, S, Liauw, J, Yu, G, Hasegawa, H, Song, YQ, Rozmahel, R, Mount, HTJ, Chen, F, Nguyen, V, St GeorgeHyslop, P, Westaway, D, Fraser, P   +17 more
openaire   +4 more sources