دورية أكاديمية
Nicotinamide Phosphoribosyltransferase Positive Allosteric Modulators Attenuate Neuronal Oxidative Stress
| العنوان: | Nicotinamide Phosphoribosyltransferase Positive Allosteric Modulators Attenuate Neuronal Oxidative Stress |
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| المؤلفون: | Jesse Gordon-Blake, Kiira Ratia, Victoria Weidig, Ganga Reddy Velma, Martha Ackerman-Berrier, Christopher Penton, Soumya Reddy Musku, Erick T.M. Alves, Tom Driver, Leon Tai, Gregory R. J. Thatcher |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biochemistry, Medicine, Cell Biology, Neuroscience, Physiology, Cancer, Infectious Diseases, Biological Sciences not elsewhere classified, sup >+, reactive oxygen species, lead efforts led, fold maximum increase, counteract oxidative stress, nampt rear channel, mitigating elevated ros, nampt ), work demonstrates, provides support, pam optimization, pam binding, one approach, nicotinamide phosphoribosyltransferase, neurons stressed, neuronal excitotoxicity, neurodegenerative diseases, neurodegenerative disease, induced ros, first time, early hit, 22 cells |
| الوصف: | Evidence supports boosting nicotinamide adenine dinucleotide (NAD + ) to counteract oxidative stress in aging and neurodegenerative disease. One approach is to enhance the activity of nicotinamide phosphoribosyltransferase (NAMPT). Novel NAMPT positive allosteric modulators (N-PAMs) were identified. A cocrystal structure confirmed N-PAM binding to the NAMPT rear channel. Early hit-to-lead efforts led to a 1.88-fold maximum increase in the level of NAD + in human THP-1 cells. Select N-PAMs were assessed for mitigation of reactive oxygen species (ROS) in HT-22 neuronal cells subject to inflammatory stress using tumor necrosis factor alpha (TNFα). N-PAMs that increased NAD + more effectively in THP-1 cells attenuated TNFα-induced ROS more effectively in HT-22 cells. The most efficacious N-PAM completely attenuated ROS elevation in glutamate-stressed HT-22 cells, a model of neuronal excitotoxicity. This work demonstrates for the first time that N-PAMs are capable of mitigating elevated ROS in neurons stressed with TNFα and glutamate and provides support for further N-PAM optimization for treatment of neurodegenerative diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Nicotinamide_Phosphoribosyltransferase_Positive_Allosteric_Modulators_Attenuate_Neuronal_Oxidative_Stress/25058373Test |
| DOI: | 10.1021/acsmedchemlett.3c00391.s001 |
| الإتاحة: | https://doi.org/10.1021/acsmedchemlett.3c00391.s001Test https://figshare.com/articles/journal_contribution/Nicotinamide_Phosphoribosyltransferase_Positive_Allosteric_Modulators_Attenuate_Neuronal_Oxidative_Stress/25058373Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.3A750FB |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acsmedchemlett.3c00391.s001 |
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