Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson's disease.

Autor:	Turconi G; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland., Alam F; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland., SenGupta T; Department of Microbiology, Oslo University Hospital PO Box 0424 Oslo, Norway and University of Oslo, The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway., Pirnes-Karhu S; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland., Olfat S; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland., Schmidt MS; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA., Mätlik K; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland., Montaño-Rodriguez A; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland., Heiskanen V; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland., Garton D; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland., Piepponen PT; Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, Viikinkaari 5E, 00014, University of Helsinki, Helsinki, Finland., Brenner C; Department of Diabetes & Cancer Metabolism, City of Hope National Medical Center, Duarte, CA, USA., Holmberg CI; Medicum, Department of Biochemistry and Developmental Biology, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland., Nilsen H; Department of Microbiology, Oslo University Hospital PO Box 0424 Oslo, Norway and University of Oslo, The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, Norway., Pirinen E; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, 00290, Finland.; Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu, FIN-90220, Oulu, Finland.; Medical Research Center Oulu, Oulu University Hospital and University of Oulu Finland, Finland.; Biocenter Oulu, University of Oulu, Oulu, Finland., Andressoo JO; Department of Pharmacology, Faculty of Medicine, Haartmaninkatu 8, 00014, University of Helsinki, Helsinki, Finland.; Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society (NVS), 14183, Karolinska Institutet, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Jul 09; Vol. 10 (14), pp. e34355. Date of Electronic Publication: 2024 Jul 09 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e34355
Abstrakt:	Parkinson's disease (PD) is associated with a reduction in 26/20S proteasome and mitochondrial function and depletion of dopamine. Activation of mitochondrial function with the NAD + precursor nicotinamide riboside (NR) is a potential therapeutic for PD. However, despite recently started clinical trials, analysis of NR in mammalian animal PD models is lacking and data in simpler PD models is limited. We analyzed the effect of NR in C. elegans and in mouse 26/20S proteasome inhibition models of PD. In C. elegans , NR rescued α-synuclein overexpression induced phenotypes likely by activating the mitochondrial unfolded protein response. However, in a proteasome inhibitor-induced mouse model of PD, NR first partially rescued behavioural dysfunction, but later resulted in decrease in dopamine and its related gene expression in the substantia nigra. Our results suggest that reduction in 26/20S function with long term NR treatment may increase risk for developing reduced nigrostriatal DA function. Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles Brenner reports a relationship with ChromaDex Inc that includes: consulting or advisory and equity or stocks. Charles Brenner reports a relationship with Athena Therapeutics that includes: equity or stocks. Charles Brenner reports a relationship with Juvenis that includes: equity or stocks. Eija Pirinen reports a relationship with ChromaDex Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 Published by Elsevier Ltd.)
Databáze:	MEDLINE
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