The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson's Disease.

TitleThe NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC and Fly Models of Parkinson's Disease.
Publication TypeJournal Article
Year of Publication2018
AuthorsSchöndorf, DC, Ivanyuk, D, Baden, P, Sanchez-Martinez, A, De Cicco, S, Yu, C, Giunta, I, Schwarz, LK, Di Napoli, G, Panagiotakopoulou, V, Nestel, S, Keatinge, M, Pruszak, J, Bandmann, O, Heimrich, B, Gasser, T, Whitworth, AJ, Deleidi, M
JournalCell Rep
Volume23
Issue10
Pagination2976-2988
Date Published2018 Jun 05
ISSN2211-1247
Abstract

While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease. We report that increasing NAD+ via the NAD+ precursor nicotinamide riboside (NR) significantly ameliorates mitochondrial function in patient neurons. Human neurons require nicotinamide phosphoribosyltransferase (NAMPT) to maintain the NAD+ pool and utilize NRK1 to synthesize NAD+ from NAD+ precursors. Remarkably, NR prevents the age-related dopaminergic neuronal loss and motor decline in fly models of GBA-PD. Our findings suggest NR as a viable clinical avenue for neuroprotection in PD and other neurodegenerative diseases.

DOI10.1016/j.celrep.2018.05.009
Alternate JournalCell Rep
Citation Key10.1016/j.celrep.2018.05.009
PubMed ID29874584