The scientific study entitled “Nicotinamide riboside first alleviates symptoms but later downregulates dopamine metabolism in proteasome inhibition mouse model of Parkinson’s disease,” published in Heliyon, provides a comprehensive examination of the effects of nicotinamide riboside (NR) on Caenorhabditis elegans and mouse models for Parkinson’s disease (PD). The study emphasizes the initial therapeutic benefits of NR, demonstrating its capacity to alleviate PD-related symptoms in C. elegans overexpressing α-synuclein by improving mitochondrial function and motility. This improvement was attributed to the activation of the mitochondrial unfolded protein response (UPRmt). These findings indicate NR’s potential to counteract mitochondrial dysfunction and α-synuclein toxicity, which are hallmark features of PD pathology. Additionally, in the proteasome inhibitor induced mouse model for PD, NR administration initially mitigated behavioral deficits associated with PD, partially alleviating the disease symptoms. However, the research emphasizes a critical and novel aspect related to the long-term effects of NR, where extended treatment led to a pronounced decrease in dopamine levels and downregulation of dopamine metabolism-related gene expression in the substantia nigra, a brain region critically affected in PD. Thus, proteasome dysfunction in combination with NR treatment may increase risk for reduced nigrostriatal dopamine function in mice.
In summary, these results suggest a dualistic nature of NR’s impact, where it offers short-term neuroprotective benefits but may exacerbate dopaminergic neuron dysfunction with prolonged use in animals. Consequently, the study underscores the necessity for caution and rigorous monitoring in long-term NR treatment, highlighting the complexity of therapeutic interventions in neurodegenerative diseases. This research not only elucidates the potential short-term benefits and long-term risks associated with NR but also contributes to the broader understanding of PD treatment dynamics, thereby providing advice for future clinical applications and therapeutic strategies.
Leave a Reply