Results 221 to 230 of about 3,440,527 (298)

SCTR–Expressing Astrocyte–Serotonergic Neuron Signaling Drives Sexual Dimorphism in Depression Through KAT7/H4ac–Foxc2 Epigenetic Axis in an AMPK‐Dependent Manner

open access: yesAdvanced Science, EarlyView.
Astrocytic SCTR modulates depressive‐related phenotypes via AMPKα1, whereas lowered Mt1 blunts Megalin‐dependent AMPKα2 signaling in serotonergic neurons. Diminished AMPKα2 hinders KAT7 nuclear translocation, curtails KAT7 occupancy and H4K8ac at the Foxc2 promoter, and represses Foxc2 transcription, revealing cell‐type‐specific AMPK‐linked epigenetic ...
Fantao Meng   +15 more
wiley   +1 more source

Galactokinase 1 Positively Regulates Mitochondrial Respiration by Phosphorylating TIMM13 as a Protein Kinase

open access: yesAdvanced Science, EarlyView.
GALK1 acts as a protein kinase beyond the phosphorylation of galactose. GALK1 phosphorylates TIMM13 at Y73 in the cytoplasm. This phosphorylation prevents premature oxidative folding of TIMM13 and ensures its entrance into the intermembrane space of mitochondrion, positively regulating mitochondrial respiration.
Chang Woo Ko   +5 more
wiley   +1 more source

Developmentally Guided Differentiation of Ventral Midbrain Dopaminergic Cells Validated in Proteopathy‐Based Parkinson's Disease Models

open access: yesAdvanced Science, EarlyView.
A developmentally guided protocol reproducibly specifies EN1‐positive ventral midbrain dopaminergic (vmDA) progenitors from human pluripotent stem cells and yields functional vmDA neurons. Optogenetic induction of α‐synuclein aggregation elicits selective degeneration of TH‐positive neurons in 2D cultures and 3D neurospheroids, while transplanted ...
Heechang Moon   +12 more
wiley   +1 more source

LAPTM5 Downregulation‐Driven VAMP8 Phosphorylation Impairs Autophagosome‐Lysosome Fusion and Aggravates Septic Acute Lung Injury

open access: yesAdvanced Science, EarlyView.
LAPTM5 functions as a critical molecular scaffold bridging PGAM5 and VAMP to facilitate PGAM5‐mediated dephosphorylation of VAMP8. This cascade promotes autophagosome‐lysosome fusion, restores impaired autophagic flux, and clears damaged mitochondria, thereby mitigating cellular oxidative stress and systemic inflammation.
Lang Jiang   +12 more
wiley   +1 more source

Drug Repurposing for Treating NCOR‐Related Intellectual Disability

open access: yesAdvanced Science, EarlyView.
An autism‐associated NCOR1 heterozygous mutation upregulates NRGs and activates NRG backward signaling in hypothalamic GABAergic neurons in mouse models, leading to Gabra2 downregulation and cognitive deficits, which can be therapeutically targeted by repurposing FDA‐approved drugs.
Yan Kong   +15 more
wiley   +1 more source

WFS1 Deficiency Impairs PIAS4‐Associated SUMOylation and Increases Ubiquitin‐Mediated Spermatogenesis‐Related Protein Degradation Leading to Testicular Male Infertility

open access: yesAdvanced Science, EarlyView.
The findings establish a critical role for WFS1 in human male fertility. Mechanistically, WFS1 interacts with PIAS4 to promote the SUMOylation of key spermatogenesis‐associated proteins, which in turn competitively inhibits their K48‐linked ubiquitin‐mediated degradation during spermatogenesis.
Yunchuan Tian   +14 more
wiley   +1 more source

MIIP Inhibits Colorectal Cancer Progression by Modulating Neutrophils Infiltration and Neutrophil Extracellular Trap Formation

open access: yesAdvanced Science, EarlyView.
This diagram illustrates that MIIP suppresses tumor‐associated neutrophils infiltration and NETs formation by binding to PKR, which impairs the PKR–IKKβ interaction and attenuates NF‐κB/IL‐8 axis activation, thereby inhibiting colorectal cancer progression. This mechanism highlights a promising therapeutic target for CRC patients.
Jiaxin Li   +8 more
wiley   +1 more source

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