PGC-1α, Sirtuins and PARPs in Huntington's Disease and Other Neurodegenerative Conditions: NAD plus to Rule Them All

被引：37
作者：
Lloret, Alejandro [1 ,2 ]
Beal, M. Flint [1 ]
机构：
[1] Weill Cornell Med Coll, Feil Family Brain & Mind Res Inst, 1400 York St,5th Floor,Room A-501, New York, NY 10065 USA
[2] NeuCyte Pharmaceut, 1561 Ind Rd, San Carlos, CA 94070 USA
来源：
NEUROCHEMICAL RESEARCH | 2019年 / 44卷 / 10期
关键词：
Huntington's disease; NAD(+); Nicotinamide Riboside; Sirtruins; PGC-1; alpha; PARPs; BASE EXCISION-REPAIR; ADENINE-DINUCLEOTIDE NADH; TRANSGENIC MOUSE MODEL; DNA-POLYMERASE BETA; INCREASED OXIDATIVE DAMAGE; NICOTINAMIDE RIBOSIDE; MITOCHONDRIAL DYSFUNCTION; PARKINSONS-DISEASE; MUTANT HUNTINGTIN; IN-VITRO;
D O I：
10.1007/s11064-019-02809-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In this review, we summarize the available published information on the neuroprotective effects of increasing nicotinamide adenine dinucleotide (NAD(+)) levels in Huntington's disease models. We discuss the rationale of potential therapeutic benefit of administering nicotinamide riboside (NR), a safe and effective NAD(+) precursor. We discuss the agonistic effect on the Sirtuin1-PGC-1 alpha-PPAR pathway as well as Sirtuin 3, which converge in improving mitochondrial function, decreasing ROS production and ameliorating bioenergetics deficits. Also, we discuss the potential synergistic effect of increasing NAD+ combined with PARPs inhibitors, as a clinical therapeutic option not only in HD, but other neurodegenerative conditions.
引用
收藏
页码：2423 / 2434
页数：12
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