التفاصيل البيبلوغرافية
| العنوان: |
Calcineurin determines toxic versus beneficial responses to alpha-synuclein |
| المؤلفون: |
Pavan K. Auluck, Hanna Kim, Xiaohui Yan, Gabriela Caraveo, Kim A. Caldwell, Martin Soste, Paola Picotti, Chee Yeun Chung, Valeriya Baru, Luke Whitesell, Eugene V. Mosharov, David T. Yue, Manu Ben-Johny, Guy A. Caldwell, David Sulzer, Susan Lindquist |
| المصدر: |
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Proceedings of the National Academy of Sciences of the United States of America |
| سنة النشر: |
2014 |
| مصطلحات موضوعية: |
Lewy Body Disease, Saccharomyces cerevisiae Proteins, Calcineurin Inhibitors, Models, Neurological, Phosphatase, Mice, Transgenic, Saccharomyces cerevisiae, Biology, Tacrolimus, Mice, chemistry.chemical_compound, Calmodulin, Animals, Humans, Calcium Signaling, Cells, Cultured, Neuroinflammation, Calcium signaling, Neurons, Alpha-synuclein, Synucleinopathies, Multidisciplinary, NFATC Transcription Factors, Calcineurin, Parkinson Disease, NFAT, Phosphoric Monoester Hydrolases, Recombinant Proteins, Rats, 3. Good health, PNAS Plus, chemistry, Biochemistry, Gene Knockdown Techniques, alpha-Synuclein |
| الوصف: |
Significance Ca 2+ homeostasis is indispensable for the well being of all living organisms. Ca 2+ homeostasis is disrupted by α-synuclein (α-syn), whose misfolding plays a major role in neurodegenerative diseases termed synucleinopathies, such as Parkinson disease. We report that α-syn can induce sustained and highly elevated levels of cytoplasmic Ca 2+ , thereby activating a calcineurin (CN) cascade that results in toxicity. CN is a highly conserved Ca 2+ –calmodulin (CaM)-dependent phosphatase critical for sensing Ca 2+ concentrations and transducing that information into cellular responses. Limiting, but not eliminating, the availability of CaM, CN and/or CN substrates directly with genetic or pharmacological tools shifts the α-syn–induced CN cascade to a protective mode. This has mechanistic implications for CN's activity and provides a therapeutic venue for the treatment of synucleinopathies. |
| DOI: |
10.1073/pnas.1413201111 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f46c8de704119b87b68c5f978fff703a |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....f46c8de704119b87b68c5f978fff703a |
| قاعدة البيانات: |
OpenAIRE |