Results 101 to 110 of about 48,911 (292)

Endoplasmic reticulum proteostasis impairment in aging [PDF]

, 2017
Summary Perturbed neuronal proteostasis is a salient feature shared by both aging and protein misfolding disorders. The proteostasis network controls the health of the proteome by integrating pathways involved in protein synthesis, folding, trafficking ...
Hetz, Claudio, Felipe Cabral‐Miranda, Juan P. Vivar, Claudia Duran‐Aniotz, Cabral‐Miranda, Felipe, Duran‐Aniotz, Claudia, Claudio Hetz, Durán Aniotz, Claudia, Gabriela Martínez, Hetz Flores, Claudio, Martínez, Gabriela, Martínez Bravo, Gabriela, Cabral Miranda, Felipe, Vivar, Juan P.   +13 more
core   +1 more source

Structural Polymorphism of polyG Inclusions Revealed by In Situ Cryo‐Electron Tomography

Advanced Science, EarlyView.
Correlative cryo‐electron tomography in primary cortical neurons and NIID mouse brain tissue reveals that polyG inclusions are interconnected ribbon‐like assemblies rather than canonical amyloid fibrils. Multiple compartment‐specific ribbon states show distinct 26S proteasome accessibility, while cytoplasmic ribbons contact and deform ER‐like ...
Yunwen Qian, Yalan Wan, Chen Chen, Xiaoyu Zheng, Wenjing Du, Junhan Yang, Zhihao Quan, Biyu Yang, Jiaxi Yu, Jie Zheng, Zhaoxia Wang, Jianwen Deng, Qiang Guo   +12 more
wiley   +1 more source

TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk

Hepatology, EarlyView., 2022
The systematic approach in elucidating the gain‐of‐function (GOF) roles of TP53 mutations in early liver carcinogenesis. Unique downstream targets of TP53 L3 mutations were identified from chormatin immunoprecipitation sequencing in HCC cell lines, followed by a series of validation assays to substantiate the exclusive transcriptional regulations ...
Yin Kau Lam, Jianqing Yu, Hao Huang, Xiaofan Ding, Alissa M. Wong, Howard H. Leung, Anthony W. Chan, Kelvin K. Ng, Mingjing Xu, Xin Wang, Nathalie Wong   +10 more
wiley   +1 more source

Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin

eLife, 2018
We systematically and quantitatively evaluate whether endoplasmic reticulum (ER) proteostasis factors impact the mutational tolerance of secretory pathway proteins.
Angela M Phillips, Michael B Doud, Luna O Gonzalez, Vincent L Butty, Yu-Shan Lin, Jesse D Bloom, Matthew D Shoulders   +6 more
doaj   +1 more source

PolyG Fibrils Coalesce Into Nuclear Ribbons That Engage Proteostasis Machinery in Neuronal Intranuclear Inclusion Disease

Advanced Science, EarlyView.
In NIID, expanded NOTCH2NLC repeats give rise to nuclear polyG inclusions. Tracer‐guided in situ cryo‐electron tomography enables cross‐scale structural analysis from mouse brain to native neuronal nuclei, revealing dense‐core/peripheral‐halo inclusions built from compact polyG ribbons.
Hui Dong, Yongcheng Pan, Zhiyao Tang, Yuxuan Yao, Guicong Zhang, Junpu Wang, Haonan Xiao, Yun Tian, Beisha Tang, Dan Li, Qiang Guo, Ruijun Tian, Qiong Liu, Cong Liu   +13 more
wiley   +1 more source

Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption

eLife
Protein aggregation increases during aging and is a pathological hallmark of many age-related diseases. Protein homeostasis (proteostasis) depends on a core network of factors directly influencing protein production, folding, trafficking, and degradation.
John Yong, Jacqueline E Villalta, Ngoc Vu, Matthew A Kukurugya, Niclas Olsson, Magdalena Preciado López, Julia R Lazzari-Dean, Kayley Hake, Fiona E McAllister, Bryson D Bennett, Calvin H Jan   +10 more
doaj   +1 more source

QRICH1 Disrupts Endoplasmic Reticulum Homeostasis and Amplifies NF‐κB Signaling in Periodontal Ligament Stem Cells to Exacerbate Diabetic Periodontitis

Advanced Science, EarlyView.
QRICH1 has been established as a key factor contributing to impaired osteogenic potential and accelerated apoptosis of PDLSCs in diabetic periodontitis. QRICH1 not only significantly enhances UPR‐associated apoptotic signaling but also amplifies NF‐κB‐mediated inflammatory responses. Its inhibition restores osteogenic capacity and reduces alveolar bone
Han Li, Xiaoyu Yang, He Wang, Yunchun Kuang, Yiyao Hu, Houxuan Li, Shuhong Li, Deping Zeng, Jie Li, Jinlin Song   +9 more
wiley   +1 more source

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

Advanced 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, Wenhao Ma, Yi Zhou, Zhijie Wu, Pan Gao, Hongze Niu, Hongfei Tai, Tianyi Zhao, Zheyue Dong, Li Li, Yan Zhang, An Wang, Si Shen, Yueyang Li, Sifei Yu, Yan Peng, Wang Sheng, Xiaoyan Dong, Hua Pan, Kaibin Shi, Magdalena J. Koziol, Xiaobing Wu, Zaiqiang Zhang   +22 more
wiley   +1 more source

Proteostasis, oxidative stress and aging

, 2017
The production of reactive species is an inevitable by-product of metabolism and thus, life itself. Since reactive species are able to damage cellular structures, especially proteins, as the most abundant macromolecule of mammalian cells, systems are ...
Martín Hugo, Tobias Jung, Daniela Weber, Ioanna Korovila, José Pedro Castro, Tilman Grune, Annika Höhn   +6 more
core   +1 more source

In Situ Profiling of Nanoscale Strains Uncovers Mechano‐Architectural Predictors of Aging and Osteoarthritis Emergence

Advanced Science, EarlyView.
In situ mechanical loading of osteoarthritis‐prone murine knee joints reveals that spatial alterations in subchondral plate microarchitecture precede cartilage loss and promote a shift from coordinated epiphyseal strain dissipation in healthy joints to focal subchondral strain concentration in osteoarthritis‐prone joints.
Aikta Sharma, Lucinda A. E. Evans, Lucie E. Bourne, Jishizhan Chen, Alissa L. Parmenter, Joseph Brunet, Kamel Madi, Sebastian Marussi, Andrew A. Pitsillides, Peter D. Lee, Katherine A. Staines   +10 more
wiley   +1 more source