Bioactivated Glucoraphanin Modulates Genes Involved in Necroptosis on Motor-Neuron-like Nsc-34: A Transcriptomic Study

Research on bioactive compounds has grown recently due to their health benefits and limited adverse effects, particularly in reducing the risk of chronic diseases, including neurodegenerative conditions. According to these observations, this study investigates the activity of sulforaphane (RS-GRA) o...

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書誌詳細
出版年:Antioxidants
主要な著者: Aurelio Minuti, Alessandra Trainito, Agnese Gugliandolo, Ivan Anchesi, Luigi Chiricosta, Renato Iori, Emanuela Mazzon, Marco Calabrò
フォーマット: 論文
言語:英語
出版事項: MDPI AG 2024-09-01
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オンライン・アクセス:https://www.mdpi.com/2076-3921/13/9/1111
その他の書誌記述
要約:Research on bioactive compounds has grown recently due to their health benefits and limited adverse effects, particularly in reducing the risk of chronic diseases, including neurodegenerative conditions. According to these observations, this study investigates the activity of sulforaphane (RS-GRA) on an in vitro model of differentiated NSC-34 cells. We performed a transcriptomic analysis at various time points (24 h, 48 h, and 72 h) and RS-GRA concentrations (1 µM, 5 µM, and 10 µM) to identify molecular pathways influenced by this compound and the effects of dosage and prolonged exposure. We found 39 differentially expressed genes consistently up- or downregulated across all conditions. Notably, <i>Nfe2l2</i>, <i>Slc1a5</i>, <i>Slc7a11</i>, <i>Slc6a9</i>, <i>Slc6a5</i>, <i>Sod1</i>, and <i>Sod2</i> genes were consistently upregulated, while <i>Ripk1</i>, <i>Glul</i>, <i>Ripk3</i>, and <i>Mlkl</i> genes were downregulated. Pathway perturbation analysis showed that the overall dysregulation of these genes results in a significant increase in redox pathway activity (adjusted <i>p</i>-value 1.11 × 10<sup>−3</sup>) and a significant inhibition of the necroptosis pathway (adjusted <i>p</i>-value 4.64 × 10<sup>−3</sup>). These findings suggest RS-GRA’s potential as an adjuvant in neurodegenerative disease treatment, as both increased redox activity and necroptosis inhibition may be beneficial in this context. Furthermore, our data suggest two possible administration strategies, namely an acute approach with higher dosages and a chronic approach with lower dosages.
ISSN:2076-3921