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

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-1α-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.