Results 141 to 150 of about 10,312 (257)

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

open access: yesAdvanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo   +17 more
wiley   +1 more source

Aberrant GRP78 Phase Transition Sustains Endothelial IRE1α Signaling and Drives Blood–Brain Barrier Failure in Cerebral Amyloid Angiopathy

open access: yesAdvanced Science, EarlyView.
Vascular Aβ40 corrupts GRP78 phase behavior in brain endothelial cells, sustaining IRE1α–TRAF2–JNK signaling and driving apoptosis, tight junction loss, and blood–brain barrier failure in cerebral amyloid angiopathy. Pharmacological IRE1α inhibition restores vascular integrity, reduces leakage, and improves functional outcomes, revealing a targetable ...
Honglin Zheng   +19 more
wiley   +1 more source

Intratumoral Hypoxia Triggers Mitochondrial BHLHE40 ROS Sensing Pathway to Promote Radioresistance in Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
Hypoxia triggers a dual mechanism for BHLHE40 upregulation: reactive oxygen species (ROS)‐dependent post‐translational modification and hypoxia‐inducible factor (HIF)‐dependent transcriptional activation. Under hypoxic conditions, mitochondrial BHLHE40 accumulates and senses ROS via cysteine thiol oxidation and disulfide‐linked homodimer formation ...
Jia Liu   +13 more
wiley   +1 more source

Rhoifolin Alleviates Ulcerative Colitis by Targeting NMNAT1 and Activating SIRT1‐FOXO1 Signaling to Enhance ILC3s Effector Function

open access: yesAdvanced Science, EarlyView.
Rhoifolin directly targets NMNAT1, thereby activating nicotinamide salvage pathway and promoting intracellular NAD+ biosynthesis. Elevated NAD+ levels enhance SIRT1 activity, leading to FOXO1 deacetylation and nuclear translocation. Nuclear FOXO1 subsequently binds to the IL‐22 promoter, upregulating IL‐22 transcription and potentiating ILC3 effector ...
Hongqiong Yang   +12 more
wiley   +1 more source

Ion‐Driven Regulation of Ca2+ Flow by Ti/Zn Composite Activates ERK/MAPK Signaling and Maintains Mitochondrial Homeostasis to Promote Macrophage‐Mediated Bone Regeneration

open access: yesAdvanced Science, EarlyView.
A 3D‐printed interpenetrating Ti/Zn composite enables sustained Zn2+ release to regulate intracellular Ca2+ redistribution, preserve mitochondrial homeostasis, activate ERK/MAPK signaling, and promote M2 macrophage polarization, thereby enhancing osteoimmune‐mediated bone regeneration and peri‐implant osseointegration.
Wanyi Huang   +7 more
wiley   +1 more source

ATL2 Recruits TRAK1 to Promote Mitochondrial Transport at ER–Mitochondria Contact Sites

open access: yesAdvanced Science, EarlyView.
ABSTRACT Mitochondrial transport and distribution are crucial for cellular homeostasis, yet whether and how they are regulated by endoplasmic reticulum (ER)–mitochondria contact sites remains unclear. Here, we demonstrate that the ER protein atlastin‐2 (ATL2) orchestrates mitochondrial transport and distribution by promoting assembly of the transport ...
Yiru Cheng   +9 more
wiley   +1 more source

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