| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Heliyon, Vol 10, Iss 14, Pp e34355- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2405-8440 |
| DOI: |
10.1016/j.heliyon.2024.e34355 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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