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

Neurochem Res. 2019 Oct;44(10):2423-2434. doi: 10.1007/s11064-019-02809-1. Epub 2019 May 7.

Abstract

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.

Keywords: Huntington’s disease; NAD+; Nicotinamide Riboside; PARPs; PGC-1 alpha; Sirtruins.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mitochondria / metabolism
  • NAD / metabolism
  • Neurodegenerative Diseases / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Sirtuins / metabolism*

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • NAD
  • Poly (ADP-Ribose) Polymerase-1
  • Sirtuins