Results 171 to 180 of about 83,359 (255)

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

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

Phase Separation of SF3B1 Serves as a Critical Post‐Transcriptional Regulator During Early Mouse Embryogenesis

open access: yesAdvanced Science, EarlyView.
Phase separation of SF3B1 acts as a key regulatory mechanism for dynamic alternative splicing throughout early mouse embryogenesis. Its absence triggers extensive splicing errors, which induce persistent DNA damage, defective cell cycle progression, and failed cell lineage commitment, and ultimately hinder the normal growth and development of ...
Kang Zhao   +15 more
wiley   +1 more source

Chemically Induced Proximity in Biological Modulation. [PDF]

open access: yesACS Bio Med Chem Au
Jin X, Zhou C, Zhang X.
europepmc   +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

Probing the Energy Landscape of α‐Synuclein Amyloid Fibril Formation by Systematic K‐to‐Q Mutagenesis

open access: yesAdvanced Science, EarlyView.
We use lysine‐to‐glutamine mutations to study the effect of electrostatics on the kinetics and thermodynamics of alpha‐synuclein amyloid fibril formation. We find that mutational effects map on their structural context within fibrils and identify residues that modulate the energy landscape of alpha‐synuclein self‐assembly. Our work outlines a scalable,
Antonin Kunka   +10 more
wiley   +1 more source

Engineered Transformer Base Editor with Enhanced Editing Efficiency

open access: yesAdvanced Science, EarlyView.
A highly efficient transformer base editor system achieves robust genomic editing in a humanized mouse model. This work establishes a versatile and translatable platform, opening new avenues for precision gene therapy. ABSTRACT Canonical cytosine base editors (CBEs) achieve precise C‐to‐T conversions without inducing DNA double‐strand breaks (DSBs ...
Bowen Chen   +5 more
wiley   +1 more source

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