نتایج جستجو برای: misfolded structure

تعداد نتایج: 1570813  

PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work,  using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular d...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2010
Andrey S Tsvetkov Jason Miller Montserrat Arrasate Jinny S Wong Michael A Pleiss Steven Finkbeiner

Autophagy is an intracellular turnover pathway. It has special relevance for neurodegenerative proteinopathies, such as Alzheimer disease, Parkinson disease, and Huntington disease (HD), which are characterized by the accumulation of misfolded proteins. Although induction of autophagy enhances clearance of misfolded protein and has therefore been suggested as a therapy for proteinopathies, neur...

Journal: :Journal of molecular biology 1999
T Lazaridis M Karplus

An essential requirement for theoretical protein structure prediction is an energy function that can discriminate the native from non-native protein conformations. To date most of the energy functions used for this purpose have been extracted from a statistical analysis of the protein structure database, without explicit reference to the physical interactions responsible for protein stability. ...

Journal: :Archives of neurology 2008
Claudio Soto Lisbell D Estrada

A key molecular pathway implicated in diverse neurodegenerative diseases is the misfolding, aggregation, and accumulation of proteins in the brain. Compelling evidence strongly supports the hypothesis that accumulation of misfolded proteins leads to synaptic dysfunction, neuronal apoptosis, brain damage, and disease. However, the mechanism by which protein misfolding and aggregation trigger neu...

Journal: :Cell 2003
Yoshiharu Kawaguchi Jeffrey J Kovacs Adam McLaurin Jeffery M Vance Akihiro Ito Tso-Pang Yao

The efficient clearance of cytotoxic misfolded protein aggregates is critical for cell survival. Misfolded protein aggregates are transported and removed from the cytoplasm by dynein motors via the microtubule network to a novel organelle termed the aggresome where they are processed. However, the means by which dynein motors recognize misfolded protein cargo, and the cellular factors that regu...

2017
Aaron Ciechanover Yong Tae Kwon

Protein homeostasis (proteostasis) requires the timely degradation of misfolded proteins and their aggregates by protein quality control (PQC), of which molecular chaperones are an essential component. Compared with other cell types, PQC in neurons is particularly challenging because they have a unique cellular structure with long extensions. Making it worse, neurons are postmitotic, i.e., cann...

Journal: :Proceedings of the National Academy of Sciences of the United States of America 2005
Edyta Małolepsza Michal Boniecki Andrzej Kolinski Lucjan Piela

There is a hypothesis that dangerous diseases such as bovine spongiform encephalopathy, Creutzfeldt-Jakob, Alzheimer's, fatal familial insomnia, and several others are induced by propagation of wrong or misfolded conformations of some vital proteins. If for some reason the misfolded conformations were acquired by many such protein molecules it might lead to a "conformational" disease of the org...

Journal: :Molecular pharmacology 2013
Kentaro Hotta Akihiro Nashimoto Eiji Yasumura Masafumi Suzuki Motoki Azuma Yosuke Iizumi Daisuke Shima Ryusuke Nabeshima Masaki Hiramoto Akira Okada Kumiko Sakata-Sogawa Makio Tokunaga Takumi Ito Hideki Ando Satoshi Sakamoto Yasuaki Kabe Shinichi Aizawa Takeshi Imai Yuki Yamaguchi Hajime Watanabe Hiroshi Handa

Vesnarinone is a synthetic quinolinone derivative used in the treatment of cardiac failure and cancer. It is also known to cause agranulocytosis as a side effect, which restricts its use, although the mechanism underlying agranulocytosis is not well understood. Here, we show that vesnarinone binds to valosin-containing protein (VCP), which interacts with polyubiquitinated proteins and is essent...

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