Results 121 to 130 of about 314,032 (295)

Activity-dependent release of Adenosine: a critical re-evaluation of mechanism [PDF]

open access: yes, 2008
Adenosine is perhaps the most important and universal modulator in the brain. The current consensus is that it is primarily produced in the extracellular space from the breakdown of previously released ATP.
Wall, Mark J., Dale, Nicholas
core   +1 more source

Ammonia Detoxification Inhibits Liver Metastasis by Reshaping Hepatic Microenvironment

open access: yesAdvanced Science, EarlyView.
Liver metastasis diverts aspartate into hyperactive pyrimidine synthesis, disrupting urea cycling and causing pathogenic ammonia accumulation. Ammonia dually reprograms the microenvironment by: (1) activating hepatic stellate cells (HSCs) into pro‐fibrotic metastasis‐associated fibroblasts (MAFs), and (2) suppressing anti‐tumor monocytes/macrophages ...
Sumin Sun   +5 more
wiley   +1 more source

Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability

open access: yesAdvanced Science, EarlyView.
The ER's continuous tubular network is maintained by ER‐shaping proteins whose mutation or dysregulation contributes to neurodegenerative diseases. Here, we show that ER morphology sets the speed of Ca2+ store replenishment between firing events. Disrupting ER continuity slows intra‐ER Ca2+ redistribution from extracellular refill (SOCE) sites, driving
Valentina Davi   +13 more
wiley   +1 more source

ALKBH3 m1A Demethylase Deficiency Reduces Alzheimer's Amyloid‐β Pathology

open access: yesAdvanced Science, EarlyView.
This study identifies that ALKBH3‐driven m1A demethylation orchestrates Alzheimer's disease progression by disrupting mitochondrial and synaptic homeostasis. This epitranscriptomic mechanism suppresses PINK1‐mediated mitophagy via m1A erasure, leading to mitochondrial dysfunction, oxidative stress, elevated Aβ production, and impaired microglial ...
Yueyang Li   +25 more
wiley   +1 more source

Cars2‐Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2

open access: yesAdvanced Science, EarlyView.
We demonstrate that Cars2, a cysteine catabolic enzyme in mouse iBAT, is critical for cold tolerance and brown adipocyte differentiation. Through its CPERS activity, Cars2 produces CysSSH/H2S to induce EBF2 persulfidation, promoting its interaction with PPARγ and BRG1 to enhance thermogenic gene expression.
Xin Peng   +8 more
wiley   +1 more source

GHRHR Deficiency Enhances Retinal Ganglion Cell Survival and Visual Functions in Experimental Glaucoma by Inhibiting Ferroptosis

open access: yesAdvanced Science, EarlyView.
Glaucoma, a major cause of blindness, involves retinal ganglion cell (RGC) degeneration. This study shows growth hormone‐releasing hormone receptor (GHRHR) deficiency preserves RGC survival and restores vision, unlike activation which only aids survival.
Yan Tong   +24 more
wiley   +1 more source

mGluR5 in ECCCK to BLA Circuit Modulates Depressive‐Like Phenotypes through CCK Signaling

open access: yesAdvanced Science, EarlyView.
Dysregulation of mGluR5 and CCK signaling contributes to major depressive disorder, yet circuit‐level mechanisms remain unclear. Here, the ECCCK→BLA pathway is identified as a critical regulator of affective behavior. mGluR5 modulates synaptic function and CCK signaling within this circuit, controlling stress susceptibility and depressive‐like states ...
Muhammad Asim   +4 more
wiley   +1 more source

The Trichinella Super‐Pangenome Reveals the Evolution of Encapsulation and Predicted Host–Parasite Protein Interactions

open access: yesAdvanced Science, EarlyView.
ABSTRACT The muscle capsule of Trichinella is a critical structure that impedes immune attacks and drug penetration, yet the molecular mechanisms underlying its formation remain poorly understood. Using a high‐quality super‐pangenome comprising 12 Trichinella species, we compared extensive genomic variations between encapsulating and non‐encapsulating ...
Qingbo Lv   +8 more
wiley   +1 more source

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

open access: yesBiomedicines
Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry ...
Valentina Brunetti   +6 more
doaj   +1 more source

Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid‐β Production and Cognitive Dysfunctions in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
This study explores the opposing effects of the mGluR2 and mGluR3 receptors on amyloid precursor protein processing. mGluR2 promotes amyloidogenic cleavage, while mGluR3 favors non‐amyloidogenic pathways. Using a brain‐penetrant nanobody as a mGluR2 positive allosteric modulator, the study uncovers how its chronic activation aggravates amyloid‐β burden
Pierre‐André Lafon   +21 more
wiley   +1 more source

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