Results 111 to 120 of about 249,259 (283)

Phosphorylation‐Facilitated CKB Lactylation At K11 By GCN5 Enhances Creatine Kinase Activity and Mitigates Neuronal Damage After Cerebral Ischemia‐Reperfusion

open access: yesAdvanced Science, EarlyView.
This study uncovers hierarchical coordination between K11 lactylation and S199 phosphorylation of CKB in cerebral ischemia‐reperfusion injury. Such dual modifications potentiate CKB enzymatic function, remodel energy metabolism, alleviate oxidative stress and neuronal damage, and represent a viable therapeutic target for stroke treatment.
Chao Duan   +17 more
wiley   +1 more source

Disrupted TFEB/GDNF–cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice

open access: yesAdvanced Science, EarlyView.
ABSTRACT The LRRK2 G2019S mutation, a Parkinson's disease–linked variant, has been associated with depression‐like phenotypes, but mechanisms remain unclear. We chart age‐dependent behavioral changes and astrocyte reactivity in G2019S mice and define a pathway connecting LRRK2 to TFEB/GDNF signaling, cellular energetics, and inflammation.
Longping Yao   +5 more
wiley   +1 more source

Sulfonyl fluoride analogues as activity-based probes for serine proteases.

open access: yes, 2012
Enriched with fluoride: To expand on the available tools to interrogate proteases, we explored sulfonyl fluorides as activity-based probes. An alkyne-tagged sulfonyl fluoride covalently modifies members of the S1 family of serine proteases.
Gu, C.   +11 more
core   +1 more source

UDP‐Glucose‐6‐Dehydrogenase Mediated O‐GlcNAcylation of Tight Junction Protein 1 Suppresses Metastasis in Renal Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
Our research unveiled a regulatory paradigm wherein TRIM25 orchestrates the ubiquitin‐mediated degradation of UGDH. UGDH modulates the protein stability of TJP1 by regulating O‐GlcNAcylation levels, effectively impeding the metastasis of ccRCC. Our insights elevate UGDH to a pivotal biomarker and tumor suppressor, marking the first demonstration that ...
Xiaolin Chen   +13 more
wiley   +1 more source

Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology

open access: yes, 2011
Analysis of vertebrate genome sequences at the turn of the millennium revealed that a vastly larger repertoire of enzymes execute proteolytic cleavage reactions within the pericellular and extracellular environments than was anticipated from biochemical
Thomas H. Bugge, Roman Szabo
core   +1 more source

Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)‐Linked Neuroinflammation

open access: yesAdvanced Science, EarlyView.
Molecular editing of bilobalide uncovers BB56, a PREP‐engaging chemotype with enhanced anti‐inflammatory activity in microglia. Integrated CETSA‐MS, SAR, and pathway analyses link BB56 to attenuation of p38 MAPK/NF‐κB and NLRP3‐associated inflammatory signaling, highlighting bilobalide editing as a strategy for developing neuroinflammation‐modulating ...
Chanin Sillapachaiyaporn   +20 more
wiley   +1 more source

Serine Proteases of Parasitic Helminths

open access: yesThe Korean Journal of Parasitology, 2015
Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization.
Yang, Yong   +6 more
openaire   +2 more sources

Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity

open access: yesAdvanced Science, EarlyView.
This study identifies synapse‐enriched deubiquitinase UCHL1 as an early Aβ‐responsive regulator of retinal synaptopathy in Alzheimer's disease. Retinal UCHL1 loss accompanies excitatory synapse degeneration, p75NTR activation, and neuroinflammation, and predicts Braak stage and cognitive decline. Aβ42 fibrils trigger synaptic and UCHL1 depletion before
Altan Rentsendorj   +25 more
wiley   +1 more source

RPLP2 Mediates the Beneficial Effects of Exercise on Stress Resistance Through Muscle–Brain Communication

open access: yesAdvanced Science, EarlyView.
A novel exercise‐inducible myokine acidic ribosomal protein P2 (RPLP2), initially identified from human trials, is presented here, whose circulating levels negatively correlate with clinical anxiety severity. Muscle‐derived RPLP2 enhances hippocampal ribosomal assembly and adult neurogenesis to rescue stress‐induced anxiety deficits.
Peiyu Luo   +18 more
wiley   +1 more source

EphB1‐Mediated Transient Blood‐Brain Barrier Opening Facilitates a Ferritin‐Based Nanotherapeutic for Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
We constructed a brain‐targeted AFn‐DPZ nanodrug delivery system and identified EphB1 as its receptor on the blood‐brain barrier (BBB). This system facilitates drug transport across the BBB and thereby ameliorates cognitive impairment in Alzheimer's disease.
Shilin Wen   +5 more
wiley   +1 more source

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