The NAD+ precursor nicotinamide riboside rescues mitochondrial defects and neuronal loss in iPSC and fly models of Parkinson’s disease

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cell reports. - 23, 10 (2018) , 2976-2988, ISSN: 2211-1247

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Schöndorf, David ; Ivanyuk, Dina ; Baden, Pascale ; Sanchez-Martinez, Alvaro ; De Cicco, Silvia ; Yu, Cong ; Giunta, Ivana ; Schwarz, Lukas Kristoffer ; Di Napoli, Gabriele ; Panagiotakopoulou, Vasiliki ; Nestel, Sigrun ; Keatinge, Marcus ; Pruszak, Jan ; Bandmann, Oliver ; Heimrich, Bernd ; Gasser, Thomas ; Whitworth, Alexander J. ; Deleidi, Michela

Further information

• DOI: 10.1016/j.celrep.2018.05.009
• URN: urn:nbn:de:bsz:25-freidok-1471086
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 11:02 AM CEST