التفاصيل البيبلوغرافية
| العنوان: |
Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency |
| المؤلفون: |
Alavian, Kambiz N, Dworetzky, Steven I, Bonanni, Laura, Zhang, Ping, Sacchetti, Silvio, Mariggio, Maria A, Onofrj, Marco, Thomas, Astrid, Li, Hongmei, Mangold, Jamie E, Signore, Armando P, DeMarco, Ulrike, Demady, Damon R, Nabili, Panah, Lazrove, Emma, Smith, Peter J S, Gribkoff, Valentin K, Jonas, Elizabeth A |
| سنة النشر: |
2012 |
| المجموعة: |
University of Southampton: e-Prints Soton |
| الوصف: |
Cellular stress or injury can result in mitochondrial dysfunction, which has been linked to many chronic neurological disorders including amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Stressed and dysfunctional mitochondria exhibit an increase in large conductance mitochondrial membrane currents and a decrease in bioenergetic efficiency. Inefficient energy production puts cells, and particularly neurons, at risk of death when energy demands exceed cellular energy production. Here we show that the candidate ALS drug dexpramipexole (DEX; KNS-760704; ((6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine) and cyclosporine A (CSA) inhibited increases in ion conductance in whole rat brain-derived mitochondria induced by calcium or treatment with a proteasome inhibitor, although only CSA inhibited calcium-induced permeability transition in liver-derived mitochondria. In several cell lines, including cortical neurons in culture, DEX significantly decreased oxygen consumption while maintaining or increasing production of adenosine triphosphate (ATP). DEX also normalized the metabolic profile of injured cells and was protective against the cytotoxic effects of proteasome inhibition. These data indicate that DEX increases the efficiency of oxidative phosphorylation, possibly by inhibition of a CSA-sensitive mitochondrial conductance. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
Alavian, Kambiz N, Dworetzky, Steven I, Bonanni, Laura, Zhang, Ping, Sacchetti, Silvio, Mariggio, Maria A, Onofrj, Marco, Thomas, Astrid, Li, Hongmei, Mangold, Jamie E, Signore, Armando P, DeMarco, Ulrike, Demady, Damon R, Nabili, Panah, Lazrove, Emma, Smith, Peter J S, Gribkoff, Valentin K and Jonas, Elizabeth A (2012) Effects of dexpramipexole on brain mitochondrial conductances and cellular bioenergetic efficiency. Brain Research, 1446, 1-11. |
| الإتاحة: |
https://eprints.soton.ac.uk/334084Test/ |
| رقم الانضمام: |
edsbas.4ADD4472 |
| قاعدة البيانات: |
BASE |
