Results 171 to 180 of about 140,143 (264)

A Second Pathogenic Protein, PolyGN2C‐iso2, Reveals a Dual‐Protein Pathology in Neuronal Intranuclear Inclusion Disease

open access: yesAdvanced Science, EarlyView.
This study reveals that NOTCH2NLC transcript variant 2 generates PolyGN2C‐iso2, an aggregating protein present within intranuclear inclusions of NIID patient tissues. A novel mouse model expressing PolyGN2C‐iso2 recapitulates white matter abnormalities and cognitive deficits, mechanistically linked to mitochondrial dysfunction. These findings support a
Kang Zhang   +22 more
wiley   +1 more source

Pasta, a Versatile Transcriptomic Clock, Maps the Chemical and Genetic Determinants of Aging and Rejuvenation

open access: yesAdvanced Science, EarlyView.
Pasta is a transcriptomic aging clock built on an age‐shift learning framework and trained on 17 000 samples across 21 datasets. It accurately predicts relative biological age across tissues, platforms, and species, captures stemness‐to‐senescence transitions, and identifies age‐modulatory perturbations.
Jérôme Salignon   +6 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

A Blood‐Derived Factor Rescues ALS: Platelet Factor 4 Activates OPTN‐Dependent Autophagy to Clear SOD1 Aggregates Independently of PINK1

open access: yesAdvanced Science, EarlyView.
Systemic platelet factor 4 (PF4) is significantly depleted in amyotrophic lateral sclerosis (ALS). Peripheral PF4 replenishment restores central proteostasis by driving OPTN‐dependent, PINK1‐independent selective autophagy in motor neurons. This intervention effectively clears toxic SOD1 aggregates, blunts glial activation, and preserves neuromuscular ...
Qingjian Xie   +12 more
wiley   +1 more source

Genetic Ablation and Multi‐Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models

open access: yesAdvanced Science, EarlyView.
Genetic ablation of Cep55 in Pten‐deficient mouse models delays tumorigenesis. Integrated multi‐omics analyses (proteomics, phosphoproteomics, and spatial transcriptomics) reveal that CEP55 regulates oncogenic signaling (RAS/ERK, PI3K/AKT), integrin/FAK‐mediated adhesion, extracellular matrix (ECM) remodeling, and endocytosis.
Behnam Rashidieh   +22 more
wiley   +1 more source

Home - About - Disclaimer - Privacy