Results 131 to 140 of about 255,378 (313)

Inhibition of the Mechanistic Target of Rapamycin (mTOR)–Rapamycin and Beyond [PDF]

Cold Spring Harbor Perspectives in Medicine, 2016
Rapamycin is a Food and Drug Administration (FDA)-approved immunosuppressant and anticancer agent discovered in the soil of Easter Island in the early 1970s. Rapamycin is a potent and selective inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, which acts as a central integrator of nutrient signaling pathways.
openaire   +2 more sources

Restriction of Individual Branched‐Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice

Advanced Science, EarlyView.
Protein restriction (PR) slows Alzheimer's disease (AD) in mice, and other benefits of PR are due to decreased branched‐chain amino acids (BCAAs). We show that restricting any BCAA has benefits, with sex‐ and BCAA‐specific impacts on pathology, molecular signaling, and cognition.
Reji Babygirija, Cara L. Green, Michelle M. Sonsalla, Izabelle Marie F. Le, Fan Xiao, Sarah Yandell, Mariah F. Calubag, Michaela E. Trautman, Anna Tobon, Ryan Matoska, Chung‐Yang Yeh, Charles I. Opara, Isaac Grunow, Diana Vertein, Sophia Schlorf, Bailey A. Knopf, Michael J. Rigby, David A. Harris, Mark P. Keller, Alan D. Attie, Luigi Puglielli, Cholsoon Jang, Dudley W. Lamming   +22 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

Advanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong, Yuhang Xie, Zhijie Weng, Yongzhi Wu, Longjiang Li, Bo Li   +5 more
wiley   +1 more source

Multifaceted aging and rapamycin

Aging, 2013
Aging is commonly defined as a time-dependent loss of physiological integrity, leading to the decline and impair in organism functions and to the increase of risk for cancer and other major age-associated diseases, finally increasing vulnerability to death [1].
openaire   +2 more sources

OCIAD2 Stabilizes Integrin β1 Signaling Through SNX17‐Mediated Endosomal Recycling to Lipid Rafts and Modulates Cisplatin Response in HNSCC

Advanced Science, EarlyView.
This study identifies OCIAD2 as a critical regulator of cisplatin resistance in HNSCC. Mechanistically, OCIAD2 stabilizes integrin β1 through a direct physical interaction and facilitates its SNX17‐dependent endosomal recycling to lipid raft microdomains. Targeting OCIAD2 disrupts integrin β1 trafficking and significantly enhances cisplatin sensitivity,
Li Cui, Shanshan Si, Min Ye, Pei Lin, Meiyan Zou, Yunfan Lin, Xu Chen, Bing Guo, Wenjuan Sun, Xinyuan Zhao   +9 more
wiley   +1 more source

Developmentally Inspired, Mechanical–Metabolic Dual Gradient Osteochondral Constructs Bridging Regeneration and Therapeutic Screening

Advanced Science, EarlyView.
A developmentally inspired osteochondral construct integrates mechanical and metabolic dual gradients within a 3D‐printed platform. Human MSC spheroids are spatially directed to form cartilage–bone interfaces, enabling evaluation of regeneration without biochemical reagents and assessment of drug responses. This physiologically relevant, phase‐specific
Yurim Choi, Wonjun Jang, Raehui Kang, Ulziituya Batjargal, Jihyeon Song, Soojin Park, MinSeok Kim, Hyobum Cho, Junhyung Kim, Yu Shrike Zhang, Han‐Jun Kim, Junmin Lee   +11 more
wiley   +1 more source

Intracellular Aβ42 Sequestration by a Serine Protease Mitigates Neurotoxicity in a Drosophila Alzheimer's Disease Model

Advanced Science, EarlyView.
Emerging evidence suggests that intraneuronal Aβ accumulation represents an early pathogenic event in Alzheimer's disease (AD). Using Drosophila AD model, this study shows that a nonsecreted serine protease Yip7 physically interacts with Aβ. This causes intraneuronal Aβ accumulation but surprisingly reduces the associated neurotoxicity, arguing that ...
Jingyun Su, Meng Yang, Xinfeng Wang, Pa Wu, Zongzhao Zhai   +4 more
wiley   +1 more source

Genetic predisposition to porto‐sinusoidal vascular disorder: A functional genomic‐based, multigenerational family study

Hepatology, EarlyView., 2022
A deleterious variant of FCHSD1 results in mTOR pathway overactivation and may cause porto‐sinusoidal vascular disorder (PSVD). The pedigree of the family demonstrated an autosomal dominant disease with variable expressivity. Whole‐genome sequencing and Sanger sequencing both validated the existence of the FCHSD1 variant and the heterozygosity of c ...
Jingxuan Shan, André Megarbane, Aziz Chouchane, Deepak Karthik, Ramzi Temanni, Atilio Reyes Romero, Huiying Hua, Chun Pan, Xixi Chen, Murugan Subramanian, Chadi Saad, Hamdi Mbarek, Cybel Mehawej, Eliane Chouery, Sirin W. Abuaqel, Alexander Dömling, Sami Remadi, Cesar Yaghi, Pu Li, Lotfi Chouchane   +19 more
wiley   +1 more source

Targeted H2S Delivery System Attenuates Blood‐Spinal Cord Barrier Disruption after Spinal Cord Injury by Reshaping the Ferritinophagy Pathway

Advanced Science, EarlyView.
The αvβ3‐mediated SPRC@MPDA‐RGD targets broken endothelial cells and controllably releases SPRC. CSE is then activated to produce endogenous H2S, which inhibits ferritinophagy. In brief, H2S inhibits autophagy by activating the PI3K/Akt/mTOR pathway, thereby suppressing the ferroptosis process mediated by NCOA4, and ultimately promoting the ...
Zhiheng Chen, Xinkai Pu, Ruiyang Li, Yuezhou Wu, Qirong Zhou, Jian Wang, Yuxuan Qian, Fengjie Lu, Jian‐Yuan Zhao, Zhida Su, Jiacan Su, Xiaofeng Lian   +11 more
wiley   +1 more source

Targeted Mitochondrial ECSIT Overexpression Attenuates MASH by Increasing OTUD3 Expression

Advanced Science, EarlyView.
Mitochondrial ECSIT expression is reduced during MASH pathogenesis. Overexpression of mitochondrial ECSIT mitigates steatohepatitis and maintains hepatic metabolic homeostasis. Mechanistically, ECSIT enhances intramitochondrial OTUD3 expression to stabilize SIRT3 through deubiquitination, thus preserving mitochondrial function and impeding disease ...
Yuqing Jiang, Tingting Tong, Pengxi Shi, Xiaofan Chen, Chenhao Wang, Qingyuan Weng, Sihan Chen, Linli Que, Qi Chen, Yuehua Li, Qiang Zhu, Jiantao Li   +11 more
wiley   +1 more source