Results 91 to 100 of about 72,467 (253)

A Small‐Molecule DEPTAC Rescues Cognitive Deficits by Targeted Dephosphorylation of Pathological Tau

Advanced Science, EarlyView.
TP2 is a fully synthetic small‐molecule dephosphorylation‐targeting chimera that recruits endogenous PP2A‐Bα to Tau, enabling targeted removal of pathological phosphate modifications. In two tauopathy mouse models, systemic TP2 reduces Tau pathology, preserves neuronal and synaptic integrity, improves neuroimmune homeostasis, and rescues cognition ...
Fei Sun, Yang Liu, Qiuzhi Zhou, Qingyuan Hu, Weixia Wang, Yue Xiao, Jingfen Su, Guanting Liu, Miaomiao Sun, Lixia Chen, Hua Li, Ying Yang, Jian‐Zhi Wang   +12 more
wiley   +1 more source

UBE3A Dosage Imbalance as a Molecular Framework Linking Angelman Syndrome and Dup15q‐Associated Autism Phenotypes

American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, EarlyView.
ABSTRACT UBE3A is a dosage‐sensitive HECT E3 ubiquitin ligase whose neuronal expression is shaped by genomic imprinting at the 15q11.2‐q13 locus. Opposite directions of UBE3A dosage imbalance contribute to distinct neurodevelopmental phenotypes: loss of maternal UBE3A underlies Angelman syndrome, whereas maternally derived 15q11.2‐q13 copy‐number gains,
Ruslan Kurmashev
wiley   +1 more source

An Enzymatic Platform for Late‐Stage (Radio)isotope Labelling of Oligonucleotides With Methyltransferases

Angewandte Chemie, EarlyView.
State‐of‐the‐art synthesis of radiolabelled oligonucleotides involves multi‐step synthesis with high costs, extended timelines and significant radioactive waste generation. Herein, a dual‐methyltransferase platform enables late‐stage, site‐specific labelling, overcoming these limitations through reduced costs, faster turnaround and minimal radioactive ...
Christopher R. B. Swanson, Ulrich Kauhl, Martin R. Edelmann, Florian P. Seebeck   +3 more
wiley   +2 more sources

Therapy for Myhre Syndrome: Goals, Misconceptions, and Current Agents

American Journal of Medical Genetics Part C: Seminars in Medical Genetics, EarlyView.
ABSTRACT Myhre Syndrome (MYHRS, MIM #139210) is a rare, multisystem connective tissue disorder caused by recurrent heterozygous gain‐of‐function pathogenic variants in the SMAD4 gene, a key player in TGF‐β signaling and a regulator of extracellular matrix homeostasis.
Alessandro De Falco, Alfonso Manuel D'Alessio, Nicola Brunetti‐Pierri   +2 more
wiley   +1 more source

Lipocalin‐2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high‐fat diet–fed Ob/Ob mice

Hepatology, EarlyView., 2022
Graphical summary of obesity‐induced NASH progression by LCN2 targeted to HSC activation. Abstract Background and Aims In obesity and type 2 diabetes mellitus, leptin promotes insulin resistance and contributes to the progression of NASH via activation of hepatic stellate cells (HSCs).
Kyung Eun Kim, Jaewoong Lee, Hyun Joo Shin, Eun Ae Jeong, Hye Min Jang, Yu Jeong Ahn, Hyeong Seok An, Jong Youl Lee, Meong Cheol Shin, Soo Kyoung Kim, Won Gi Yoo, Won Ho Kim, Gu Seob Roh   +12 more
wiley   +1 more source

Multicomponent Stapling of Glucagon‐Like Peptide‐1 Enables Receptor‐Guided PROTAC Delivery

Angewandte Chemie, EarlyView.
We report a stapled glucagon‐like peptide‐1 (GLP‐1) analogue created via multicomponent tryptophan‐mediated Petasis reaction (TMPR). This strategy yields a stabilised peptide with superior helicity and improved potency. Conjugation to a bromodomain‐containing protein 4 (BRD4) degrader creates the first GLP‐1‐guided targeted protein degrader (PROTAC ...
Jan L. Venne, Sona Krajcovicova, Graeme Davies, Hannah Bolt, Jefferson Revell, David R. Spring   +5 more
wiley   +2 more sources

Genome‐wide network analysis identifies the lncRNA‐92467/miR‐205‐5p/PTPRM/CAMs axis in a rat model of hypoxic pulmonary hypertension

Animal Models and Experimental Medicine, EarlyView.
The pathogenesis of hypoxic pulmonary hypertension (HPH) remains unclear. In this study, we explored its key regulatory mechanisms using animal models, RNA sequencing, and cellular assays. We found that lncRNA‐92467 functions as a ceRNA, binding miR‐205‐5p, and thereby upregulating PTPRM, inhibiting abnormal proliferation and migration of endothelial ...
Yan‐Ying Shen, Yi‐Bing Chen, Xin Li, Xiang Xu, Ge Guo, Han‐Lu Li, Yong‐Ming Yao, Chun‐Lei Liu   +7 more
wiley   +1 more source

Nitro Reduction‐Based RNA Control and Ultrafast Release

Angewandte Chemie, EarlyView.
A chemical RNA caging–uncaging strategy based on nitro reduction is described. Nitroaryl groups introduced via acylation temporarily block the functions of diverse RNAs in vitro and in living cells. Treatment with a diboronic acid–bipyridine mixture rapidly reduces the nitro groups, releasing RNAs and restoring their activity.
Yiran Zhao, Senfeng Zhang, Junsong Guo, Tuan‐Khoa Kha, Song Chen, Chunyi Hu, Ru‐Yi Zhu   +6 more
wiley   +2 more sources

Cardiovascular Exercise Drives Neuroprotection in a Mouse Model of Spinocerebellar Ataxia 1 Via Rescue of Aberrant Splicing

Annals of Neurology, EarlyView.
Objective Spinocerebellar ataxia 1 (SCA1) is a fatal hereditary neurodegenerative disorder with no approved therapies, and gene‐targeting strategies have thus far failed in clinical trials. Exercise remains the only intervention shown to provide clinical benefit in patients with spinocerebellar ataxias (SCAs), yet the underlying mechanisms remain ...
Isabel Soto, Michael Bonomo, Brianna S. Nelthrope, Benjamin D. Carr, Emma Palmer, Mariana Sierra, Ilkim Erturk, David Peppercorn, Eleonor Cox, Tiare K. Vasconcellos, Henry L. Paulson, Hannah K. Shorrock, Sharan R. Srinivasan   +12 more
wiley   +1 more source

Investigation of the activity of phosphothioate and phosphothioate-LNA-modified oligonucleotides against HIV-1

Frontiers in Medicine
This study investigated the antiretroviral efficacy, toxicity profile, and cellular uptake of phosphothioate (PS) and PS/LNA-modified oligonucleotides within an in vitro HIV infection model.
Ludmila Gotfrid, Kirill Elfimov, Maria Gashnikova, Aleksey Totmenin, Aleksandr Agaphonov, Natalya Gashnikova   +5 more
doaj   +1 more source