Results 91 to 100 of about 98,327 (230)

Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model

open access: yesAdvanced Science, EarlyView.
Emerging evidence suggests that intraneuronal Aβ accumulation represents an early pathogenic event in Alzheimer's disease (AD). Using Drosophila AD model, this study shows that a nonsecreted serine protease Yip7 physically interacts with Aβ. This causes intraneuronal Aβ accumulation but surprisingly reduces the associated neurotoxicity, arguing that ...
Jingyun Su   +4 more
wiley   +1 more source

Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility

open access: yesAdvanced Science, EarlyView.
We identify an antagonistic ubiquitin circuit that controls cellular permissiveness to multiple coronaviruses. The deubiquitinase USP7 stabilizes the epigenetic regulator KDM6A to upregulate viral receptors, while the E3 ligase RNF40 degrades KDM6A by catalyzing K6/K11‐ubiquitin chains of KDM6A for autophagic degradation.
Meng‐Zhuo Huang   +9 more
wiley   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

open access: yesAdvanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao   +16 more
wiley   +1 more source

Involvement of the Ubiquitin-Proteasome System in the Formation of Experimental Postsurgical Peritoneal Adhesions

open access: yesMediators of Inflammation, 2012
We investigated the Ubiquitin-Proteasome System (UPS), major nonlysosomal intracellular protein degradation system, in the genesis of experimental postsurgical peritoneal adhesions.
Clara Di Filippo   +7 more
doaj   +1 more source

Chaperone‐Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction

open access: yesAdvanced Science, EarlyView.
This study demonstrates that inflammatory stimuli induce the acetylation‐triggered, chaperone‐mediated autophagic degradation of ubiquitin‐specific peptidase 9 X‐linked (USP9X) in macrophages. USP9X acts as a macrophage “inflammation switch” after myocardial infarction (MI). USP9X loss destabilizes tumor necrosis factor receptor‐associated factor (TRAF)
Biqing Wang   +7 more
wiley   +1 more source

Targeted Mitochondrial ECSIT Overexpression Attenuates MASH by Increasing OTUD3 Expression

open access: yesAdvanced Science, EarlyView.
Mitochondrial ECSIT expression is reduced during MASH pathogenesis. Overexpression of mitochondrial ECSIT mitigates steatohepatitis and maintains hepatic metabolic homeostasis. Mechanistically, ECSIT enhances intramitochondrial OTUD3 expression to stabilize SIRT3 through deubiquitination, thus preserving mitochondrial function and impeding disease ...
Yuqing Jiang   +11 more
wiley   +1 more source

Elevated TRIM25 Impairs Poly (ADP‐ribose) Metabolism via PARG Degradation and Mediates Compression‐Induced Intervertebral Disc Degeneration

open access: yesAdvanced Science, EarlyView.
TRIM25 acts as a multifunctional hub driving intervertebral disc degeneration under mechanical stress. Mechanical compression significantly upregulates TRIM25 expression, establishing it as a key E3 ubiquitin ligase platform. TRIM25 targets PARG and Ku80 via distinct molecular interfaces, triggering their ubiquitination and degradation.
Zhangrong Cheng   +9 more
wiley   +1 more source

The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research

open access: yesBiomedicines
Acute kidney injury (AKI) remains a critical clinical challenge due to its complex pathophysiology and lack of targeted therapies. We hypothesize that the ubiquitin-proteasome system (UPS) and ubiquitin-like modifiers (UBLs) are not merely isolated ...
Yu Zhou, Shuchun Tao, Lei Liu, Lei Zhang
doaj   +1 more source

Cortical Somatostatin Neurons Regulate Seizure Susceptibility via MINAR1/Gαs–cAMP Signaling

open access: yesAdvanced Science, EarlyView.
Our study identifies MINAR1 as a novel regulator of cortical interneuron excitability and seizure susceptibility. MINAR1 is preferentially expressed in SST+ interneurons. Genetic ablation of MINAR1 leads to seizure hypersensitivity, reduced SST+ neuron excitability, and impaired Gαs–cAMP signaling, disrupting the E/I balance.
Wei‐Tang Liu   +20 more
wiley   +1 more source

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