Results 121 to 130 of about 949,070 (290)

Near‐Infrared Fluorescent PROTAC Enables Theranostic Imaging and Selective Tau Degradation in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
Here, we report a novel NIR fluorescent PROTAC platform that enables real‐time imaging and targeted degradation of Alzheimer's p‐Tau. Our lead compound effectively clears p‐Tau, reduces APP/Aβ, and alleviates cognitive deficits in AD mice. This work demonstrates a theranostic strategy for visualizing degradation and developing next‐generation AD ...
Ziwei Ren   +11 more
wiley   +1 more source

Effects of proteasome inhibitors on TGFBIp internalization.

open access: yes, 2015
A. Corneal fibroblasts were treated with CHX (to inhibit translation), and MG132 (proteasome inhibitors) or Baf-A1 (lysosomal inhibitors) for 60 min at 37°C, and then incubated with or without TGFBIp for 120 min at 37°C as indicated. The TGFBIp level was
Tae-im Kim (50894)   +5 more
core   +1 more source

Nrsn1–Smarcc1 Coupling Regulates Neural Stem Cell Differentiation and Chronic‐phase Recovery After Ischemic Stroke

open access: yesAdvanced Science, EarlyView.
In the post‐stroke brain, Foxa2 induces the transcriptional upregulation of Nrsn1 in NSCs. Nrsn1 functionally couples with Smarcc1, modulating its nuclear availability and protein abundance, thereby influencing Smarcc1‐associated regulatory programs linked to neuronal lineage commitment. Through this coupling, Nrsn1 promotes the differentiation of NSCs
Ruolin Zhang   +18 more
wiley   +1 more source

Proteasome inhibitors: therapeutic strategy in chronic lymphoproliferative syndrome

open access: yesActa Médica del Centro, 2016
14 years ago the first results of the clinical trials phase I with bortezomib were published, the first proteasome inhibitor; its introduction into clinical practice meant an improvement in complete remission rates, of global survival and free ...
Agnerys López Sacerio   +1 more
doaj  

Molecular Glue Degraders Enhance CAPRIN1‐Dependent Lysosomal Degradation of APP and Reduce Amyloid β in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
A new class of lysosome‐directed molecular glue degraders selectively enhance CAPRIN1–APP interactions, driving APP degradation and reducing amyloid‐β production in human neurons and Alzheimer's disease mouse models. This CAPRIN1‐dependent targeted protein degradation strategy reveals a previously unrecognized therapeutic approach for disrupting the ...
Sunghan Jung   +15 more
wiley   +1 more source

CaMKII suppresses proteotoxicity by phosphorylating BAG3 in response to proteasomal dysfunction

open access: yesEMBO Reports
Protein quality control serves as the primary defense mechanism for cells against proteotoxicity induced by proteasome dysfunction. While cells can limit the build-up of ubiquitinated misfolded proteins during proteasome inhibition, the precise mechanism
Chenliang Zhang   +7 more
doaj   +1 more source

Targeting the CRYAB/β‐Catenin Axis with an MMP‐9‐Responsive Hydrogel Disrupts CTC Clusters to Suppress Progression of Hepatocellular Carcinoma after Radiofrequency Ablation

open access: yesAdvanced Science, EarlyView.
The graphical abstract illustrates that sublethal thermal stress after iRFA upregulates the chaperone CRYAB in residual HCC cells, which stabilizes β‐catenin and drives a dual pathological program, including EMT and N2‐TAN polarization, thereby leading to heterotypic CTC cluster formation. The MMP‐9‐responsive hydrogel (XB@Gel) delivers XAV‐939 and BMS‐
Hui Chen   +8 more
wiley   +1 more source

Prion‐Like Protein LENG8‐Mediated Nucleation Drives Stress Granule Assembly

open access: yesAdvanced Science, EarlyView.
LENG8 is a newly identified stress granule (SG) nucleator required for SG assembly. Following stress, nuclear LENG8 granules disassemble, allowing LENG8 to translocate into the cytoplasm and form independent nucleation foci. These foci fuse with canonical early G3BP1/TIA1 seeds via LENG8‐TIA1 binding to drive SG maturation.
Mingxing Zhang   +6 more
wiley   +1 more source

Mutant KRAS‐m6A Epitranscriptome Axis Promotes Colorectal Cancer and is a Therapeutic Target

open access: yesAdvanced Science, EarlyView.
Mutant KRAS‐m6A axis promotes colorectal cancer (CRC) progression. Mutant KRAS stabilizes METTL3, leading to increased m6A‐modified BCL9L mRNA and translation of BCL9L protein. BCL9L in turn mediates TGF‐β secretion to induce differentiation of Treg and an immunosuppressive microenvironment.
Danyu Chen   +12 more
wiley   +1 more source

Novel Organic Proteasome Inhibitors Identified by Virtual and in Vitro Screening

open access: yes, 2016
Proteasome inhibition is a promising strategy for treating cancers. Herein, we report the discovery of novel drug-like inhibitors of mammalian proteasome 20S using a multistep structure-based virtual ligand screening strategy.
Xavier Maréchal (1720288)   +8 more
core   +1 more source

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