Results 61 to 70 of about 7,774 (200)

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

Targeted Lysosomal Degradation of Extracellular and Membrane Proteins: From Receptor Hijacking to Programmable Endolysosomal Routing

open access: yesAdvanced Science, EarlyView.
Targeted chimeric degraders engage extracellular or membrane proteins and endocytosable cell‐surface receptors, forming ternary complexes that induce receptor‐mediated internalization. Following endocytosis, post‐endocytic sorting—not internalization alone—determines target fate.
Ke Liu   +6 more
wiley   +1 more source

Activatable PROTAC nanoassembly for photodynamic PTP1B proteolysis enhances glioblastoma immunotherapy

open access: yesActa Pharmaceutica Sinica B
In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity.
Yeongji Jang   +13 more
doaj   +1 more source

Biomimetic Scaffold‐Based 3D Models for Decoding Cancer Biology and Advancing Therapy

open access: yesAdvanced Science, EarlyView.
A timeline of the research history of 3D biomimetic scaffold materials and platforms. With advances in biomimetic materials and 3D scaffold technologies, their functional scope has expanded from mimicking basic physical and biochemical properties to increasingly replicating complex pathophysiological processes.
Haitao Zhao   +10 more
wiley   +1 more source

Palmitoyl Acyltransferase Zdhhc17 Promotes Functional Recovery After Spinal Cord Injury by Targeting the Nuclear Transport Factors Kpna2 and Ipo9

open access: yesAdvanced Science, EarlyView.
In this study, we demonstrate that Zdhhc17, acting as a PAT, suppresses neuronal apoptosis and promotes axon regeneration after injury, thereby enhancing functional recovery following SCI. In this context, Kpna2 and Ipo9 serve as novel palmitoylation substrates of Zdhhc17, whose palmitoylation prevents the injury‐induced degradation of their proteins ...
Meixuan Chen   +12 more
wiley   +1 more source

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

open access: yesAdvanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang   +8 more
wiley   +1 more source

Site‐Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids

open access: yesAngewandte Chemie, EarlyView.
Genetic code expansion (GCE) enables site‐specific installation of noncanonical amino acids containing bioorthogonal conjugation handles, allowing precise, homogeneous protein modification. This review examines the principles of orthogonal translation, surveys the chemistries available for chemoselective labeling, and highlights emerging multi‐site ...
Rahul Sarkar   +2 more
wiley   +2 more sources

In Situ Bioorthogonal Synthesis of PROTACs via Dual‐Responsive Cleavage for Synergistic Photo‐Immunotherapy

open access: yesAdvanced Science, EarlyView.
A bioactive self‐delivering SNAP‐TAC platform responds to tumor‐associated cathepsin B and glutathione, enabling in situ bioorthogonal synthesis of a BRD4‐degrading proteolysis‐targeting chimera within the tumor microenvironment. The resulting BRD4 degradation and PD‐L1 downregulation synergize with photodynamic therapy‐induced immunogenic cell death ...
Shiqin Jian   +14 more
wiley   +1 more source

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition

open access: yesCell Reports Medicine
Summary: Cyclin-dependent kinases 12/13 play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Biallelic CDK12 loss has been documented in various malignancies.
Yu Chang   +29 more
doaj   +1 more source

AI‐Designed TREM1‐Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury

open access: yesAdvanced Science, EarlyView.
AI‐enabled de novo design of a TREM1 binder, integrated into a BBB‐crossing and macrophage‐targeted nanoplatform, enables TREM1 degradation and attenuates neuroinflammation, thereby promoting neuroprotection and tissue repair after traumatic brain injury. ABSTRACT Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI),
Yimin Huang   +19 more
wiley   +1 more source

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