Results 141 to 150 of about 195,005 (265)

Drug‐Induced Cuproptosis Defines the Therapeutic Window of Celecoxib in Intervertebral Disc Degeneration via the HSP90‐RBX1 Axis

open access: yesAdvanced Science, EarlyView.
This study reveals the dual role of celecoxib in intervertebral disc degeneration. While low concentrations are protective, high concentrations induce toxicity by upregulating HSP90, which synergizes with USP15 to deubiquitinate and stabilize RBX1. This leads to degradation of COMMD1/ATP7B, copper dyshomeostasis, and ultimately, cuproptosis.
Youfeng Guo   +11 more
wiley   +1 more source

Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies. [PDF]

open access: yesFront Cell Neurosci
Lines G   +5 more
europepmc   +1 more source

“Membrane‐Guided” Repair Strategy: Precision Delivery of GGT1 Degrader for Targeted Repair and Regeneration of Spinal Cord Neurons

open access: yesAdvanced Science, EarlyView.
This study confirms that GGT1 is a key driver of neuronal ferroptosis following spinal cord injury. We developed NSCm@EA, a biomimetic delivery system coated with neural stem cell membranes, for precise delivery of enocyanin to injured neurons. By combining targeted delivery with ubiquitination degradation mechanisms, this system promotes MGRN1 ...
Tao Yang   +14 more
wiley   +1 more source

Structures of the 26<i>S</i> proteasome in complex with the Hsp70 co-chaperone Bag1 reveal a mechanism for direct substrate transfer. [PDF]

open access: yesSci Adv
Maestro-López M   +10 more
europepmc   +1 more source

ZDHHC18‐Mediated Palmitoylation of ORF3a Promotes SARS‐CoV‐2 Pathogenesis by Antagonizing TRIM16‐Mediated Ubiquitination and Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
Palmitoylation by ZDHHC18 blocks ORF3a K27‐linked ubiquitination mediated by TRIM16, thereby preventing its proteasomal degradation and strengthening viral pathogenesis. Targeting palmitoylation through a pharmacological inhibitor (2‐BP), a competitive inhibitory peptide (OPIP), or adenovirus‐mediated knockdown of ZDHHC18 expression presents a ...
Sidi Yang   +17 more
wiley   +1 more source

A Plug‐and‐Play Platform for Customizing Multivalent Degraders and Degrader‐Drug Conjugates

open access: yesAdvanced Science, EarlyView.
Membrane proteins remain challenging targets for conventional TPD approaches. Here, the authors develop UPTAB, a modular platform leveraging ultrahigh‐affinity orthogonal Im/CL protein pairs for lysosomal degradation of membrane proteins. Mono‐targeted (Type‐I), dual‐targeted (Type‐II), and tri‐targeted (Type‐III) UPTABs enable simultaneous degradation
Mengqing Zhao   +7 more
wiley   +1 more source

AKT Signaling Regulates Agrin-Mediated Acetylcholine Receptor Surface Density. [PDF]

open access: yesMedicina (Kaunas)
Jaiswal N   +5 more
europepmc   +1 more source

BCMA‐Engineered Dendritic Cell‐Derived Exosomes as Bi‐Functional Therapeutics Orchestrating Cytokine Sequestration and Immune Activation for Multiple Myeloma

open access: yesAdvanced Science, EarlyView.
A dual‐function cell‐free therapeutic based on DC2.4 cell‐derived exosomes engineered to display BCMA. (Left) Soluble Ligand Sequestration (Decoy Function): DB Exo act as molecular decoys that predominantly sequester soluble APRIL with partial BAFF attenuation, effectively disrupting the NF‐κB survival signaling axis and suppressing myeloma cell ...
Yuqing Zeng   +5 more
wiley   +1 more source

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