Results 171 to 180 of about 612,165 (290)

HSP70 Interactome‐Mediated Proteolysis Targeting Chimera (HSP70‐PROTAC) for Ferroptosis‐Driven Cancer Treatment

open access: yesAdvanced Science, EarlyView.
This study reports a novel targeted protein degradation strategy termed “HSP70‐PROTAC” that recruits Hsc70 complex to a target protein for inducing degradation. Among them, GDAz‐3 exhibits effective GPX4 degradation activity via UPS/CMA processes, triggering ferroptosis‐driven anticancer activity in vitro and in vivo.
Jinyun Dong   +15 more
wiley   +1 more source

Engineered GM1 Intersects Between Mitochondrial and Synaptic Pathways to Ameliorate ALS Pathology

open access: yesAdvanced Science, EarlyView.
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease driven by genetic and molecular disruptions affecting energy balance, protein homeostasis, and stress responses in nerve cells. Studies using human and rodent models identified convergent defects in mitochondria and synaptic function.
Federica Pilotto   +11 more
wiley   +1 more source

The Evolutionarily Conserved TPM1 Super‐Enhancer Drives Skeletal Muscle Regeneration via Mechanotransduction Signaling

open access: yesAdvanced Science, EarlyView.
By integrating biomechanical and epigenetic cues, the evolutionarily conserved TPM1 super‐enhancer drives myogenesis via TEAD4‐mediated chromatin looping. This mechanism produces species‐specific outputs (linear TPM1 mRNA in mice and CircTPM1 in bovine) that activate PI3K/AKT mechanotransduction and the MYH10/MYL3 axis to execute cytoskeletal ...
Ruimen Zhang   +27 more
wiley   +1 more source

Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC‐Derived Cortical Organoids

open access: yesAdvanced Science, EarlyView.
A new cerebrocortical organoid model using isogenic hiPSCs with familial Alzheimer's mutations recapitulates key AD features, including amyloid‐beta and phospho‐Tau aggregation, neuronal hyperexcitability, and synapse loss. Single‐cell RNA‐seq reveals aberrant pathways in excitatory and inhibitory neurons.
Sergio R. Labra   +23 more
wiley   +1 more source

Targeting Microglial CD49a Inhibits Neuroinflammation and Demonstrates Therapeutic Potential for Parkinson's Disease

open access: yesAdvanced Science, EarlyView.
This study shows that integrin receptor CD49a (Itga1 gene) is significantly upregulated in hyperactivated microglia and microglia‐specific knockdown of Itga1 rescues neuroinflammation and neurodegeneration in a chronic Parkinson's disease (PD) model by targeting PGAM5‐mediated mitochondrial dysfunction and NLRP3 activation. Targeted inhibition of CD49a
Huanpeng Lu   +6 more
wiley   +1 more source

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