P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage.
P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage.
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DOI：
10.1016/j.cell.2014.07.040
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发表时间：
2014-09-11
期刊：
影响因子：
64.5
通讯作者：
McKnight SL
中科院分区：
文献类型：
--
作者：
Wang G;Han T;Nijhawan D;Theodoropoulos P;Naidoo J;Yadavalli S;Mirzaei H;Pieper AA;Ready JM;McKnight SL
The P7C3 class of aminopropyl carbazole chemicals fosters the survival of neurons in a variety of rodent models of neurodegeneration or nerve cell injury. To uncover its mechanism of action, an active derivative of P7C3 was modified to contain both a benzophenone for photo-crosslinking and an alkyne for CLICK chemistry. This derivative was found to bind nicotinamide phosphoribosyltransferase (NAMPT), the rate limiting enzyme involved in the conversion of nicotinamide into nicotinamide adenine dinucleotide (NAD). Administration of active P7C3 chemicals to cells treated with doxorubicin, which induces NAD depletion, led to a rebound in intracellular levels of NAD and concomitant protection from doxorubicin-mediated toxicity. Active P7C3 variants likewise enhanced the activity of the purified NAMPT enzyme, providing further evidence that they act by increasing NAD levels through its NAMPT-mediated salvage.
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影响因子：
7.3
作者：
Naidoo J;De Jesus-Cortes H;Huntington P;Estill S;Morlock LK;Starwalt R;Mangano TJ;Williams NS;Pieper AA;Ready JM
通讯作者：
Ready JM
影响因子：
15
作者：
MacMillan KS;Naidoo J;Liang J;Melito L;Williams NS;Morlock L;Huntington PJ;Estill SJ;Longgood J;Becker GL;McKnight SL;Pieper AA;De Brabander JK;Ready JM
通讯作者：
Ready JM
影响因子：
46.2
作者：
Pieper AA;McKnight SL;Ready JM
通讯作者：
Ready JM
影响因子：
2.8
作者：
Bandyopadhyay, Saibal;Bong, Dennis
通讯作者：
Bong, Dennis
影响因子：
25
作者：
Mack, TGA;Reiner, M;Coleman, MP
通讯作者：
Coleman, MP