Results 111 to 120 of about 381,302 (291)

Multifunctional Gold Nanocluster‐Based PROTAC System for Targeted Degradation of Phosphorylated Tau and Modulation of Neuroinflammation in Alzheimer's Disease

Advanced Functional Materials, EarlyView.
We present a novel proteolysis‐targeting chimera (PROTAC) system conjugated to lipoic acid gold nanoclusters (PLANC), designed to degrade pTau, regulate inflammatory signaling, and effectively traverse the blood‐brain barrier (BBB). PLANC degraded pTau at various phosphorylation sites, with mechanistic studies confirming proteasome‐mediated degradation
Sarah Nevins, Callan D. McLoughlin, Wan‐Kyu Ko, Hye Kyu Choi, Brandon Conklin, Joshua B. Stein, Yannan Hou, Hongwon Kim, Rohan Khulbe, Ki‐Bum Lee   +9 more
wiley   +1 more source

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

Advanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel, Sofia Kokkaliari, Qiwen Gao, Jinjing Chen, Larissa Costa de Almeida, Srinivasarao Tenneti, Derek A. Leas, Eli Levit, Lewis S. Alexander, Khalil A. Abboud, Pingrong Wei, Michael D. Cameron, James R. Rocca, Ranjala Ratnayake, Donna D. Zhang, Hendrik Luesch, Robert W. Huigens III   +16 more
wiley   +1 more source

NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets

Journal of Orthopaedic Surgery and Research
Osteoporosis is a systemic skeletal disorder characterized by reduced bone density and an increased risk of fractures, particularly prevalent in the aging population.
Heng Wu, Junhui Zuo, Yu Dai, Hairui Li, Song Wang   +4 more
doaj   +1 more source

Trans-Binding Mechanism of Ubiquitin-like Protein Activation Revealed by a UBA5-UFM1 Complex

Cell Reports, 2016
Modification of proteins by ubiquitin or ubiquitin-like proteins (UBLs) is a critical cellular process implicated in a variety of cellular states and outcomes.
Walaa Oweis, Prasanth Padala, Fouad Hassouna, Einav Cohen-Kfir, Dalton R. Gibbs, Emily A. Todd, Christopher E. Berndsen, Reuven Wiener   +7 more
doaj   +1 more source

Knowing then defeating: Ubiquitin activating enzyme, a promising target for cancer therapy

, 2020
Ubiquitin ist ein 76 Aminosäuren langes Polypeptid, das in allen Eukaryoten vorkommt und hoch konserviert ist. Ubiquitin kann Proteine modifizieren indem es mittels einer kovalente Bindung an diese angeheftet wird. Eukaryotische Zellen nutzen Ubiquitin, um fundamentale zelluläre Prozesse wie den Proteinabbau, die Immunantwort sowie die Regulation der ...
openaire   +2 more sources

Agnuside Stabilizes the Complex I Assembly Factor NDUFAF6 to Reinforce Mitochondrial Efficiency and Thermogenic Responsiveness

Advanced Science, EarlyView.
ABSTRACT Brown and beige adipocytes dissipate energy as heat, yet effective strategies to enhance their mitochondrial efficiency remain limited. Here, we identify Agnuside (AGN) as a selective stabilizer of the complex I assembly factor NDUFAF6. AGN directly binds cytosolic NDUFAF6, suppresses its ubiquitination, prolongs its half‐life, and facilitates
Qingwen Zhao, Li Xie, Qianzhuo Wang, Shuying Dai, Bei Li, Yingjuan Zhang, Zhe Sun, Yue Gao   +7 more
wiley   +1 more source

Ubiquitination of basal VEGFR2 regulates signal transduction and endothelial function

Biology Open, 2017
Cell surface receptors can undergo recycling or proteolysis but the cellular decision-making events that sort between these pathways remain poorly defined.
Gina A. Smith, Gareth W. Fearnley, Izma Abdul-Zani, Stephen B. Wheatcroft, Darren C. Tomlinson, Michael A. Harrison, Sreenivasan Ponnambalam   +6 more
doaj   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

Advanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng, Yanlin Guo, Liumi Jiang, Jing Luo, Yan Liu, Ziwei Yuan, Pingyang Ke, Ran Duan, Fei Xiao   +8 more
wiley   +1 more source

ZDHHC9‐Mediated Palmitoylation of ACSL4 Drives Ferroptosis in Diabetes Mellitus–Induced Erectile Dysfunction

Advanced Science, EarlyView.
ABSTRACT Diabetes mellitus‐induced erectile dysfunction (DMED) is a highly prevalent complication among diabetic patients; however, its underlying pathogenic mechanisms remain incompletely understood. Metabolic disorder is a hallmark of diabetes, yet its precise contribution to DMED progression is not well defined.
Wanyang Guo, Ming Xiao, Mengjun Huang, Dongzi Peng, Ruijiang Zeng, Ruilin Liu, Yuanqiao Zhao, Zhihan Ouyang, Yulong Hong, Zexian Ding, Zhuo Xing, Hao Su, Jinxiang Wang, Wenjun Mao, Xin Jin   +14 more
wiley   +1 more source

Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? [version 1; referees: 1 approved, 2 approved with reservations]

F1000Research, 2016
A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation of protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 in ALS, and tau in Alzheimer’s disease.
Daniel Ortuno, Holly J. Carlisle, Silke Miller   +2 more
doaj   +1 more source