Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson's disease
Turconi, Giorgio; Alam, Farhan; SenGupta, Tanima; Pirnes-Karhu, Sini; Olfat, Soophie; Schmidt, Mark S.; Mätlik, Kärt; Montaño-Rodriguez, Ana; Heiskanen, Vladimir; Garton, Daniel; Piepponen, Petteri T.; Brenner, Charles; Holmberg, Carina I.; Nilsen, Hilde; Pirinen, Eija; Andressoo, Jaan Olle (2024-07-09)
Elsevier
09.07.2024
Giorgio Turconi, Farhan Alam, Tanima SenGupta, Sini Pirnes-Karhu, Soophie Olfat, Mark S. Schmidt, Kärt Mätlik, Ana Montaño-Rodriguez, Vladimir Heiskanen, Daniel Garton, Petteri T. Piepponen, Charles Brenner, Carina I. Holmberg, Hilde Nilsen, Eija Pirinen, Jaan-Olle Andressoo, Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson's disease, Heliyon, Volume 10, Issue 14, 2024, e34355, ISSN 2405-8440, https://doi.org/10.1016/j.heliyon.2024.e34355
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2024 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2024 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://creativecommons.org/licenses/by-nc-nd/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202408195485
https://urn.fi/URN:NBN:fi:oulu-202408195485
Tiivistelmä
Abstract
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.
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.
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