In silico analysis of nicotine’s molecular targets in Parkinson’s disease

We aimed to elucidate the molecular processes involved in how nicotine affects PD.Toxicogenomic, molecular mechanisms, physicochemical properties, pharmacokinetic profile, and biological activity were analysed.We found that the therapeutic potential of nicotine in PD may be attributed to its ability to modulate the expression of 38 genes, especially GAPDH, TNF, IL6, and BDNF. The molecular mechanisms underlying the protective effects of nicotine against PD involve several pathways, including the ‘Parkinson’s disease pathway’, ‘the selenium micronutrient network’, ‘the oxidative stress response’, ‘dopamine binding’, ‘Parkinsonian disorders’, and ‘Lewy body disease’. miRNAs like hsa-miRNA-203a-3p and miRNA-26b-5p and transcription factors like HNF4, MAPK3, and EVI1 explained how nicotine protects neurons from PD.An assessment was also carried out on drug candidates (polaprezinc) and miRNA sponges (hsa-miR-181a-5p, hsa-miR-124-3p, hsa-miR-1-3p) that may possess the capability to synergize the effects of nicotine. Nicotine’s physicochemical properties, pharmacokinetic profile, and biological activity are conducive to its favourable attributes in the context of PD, including high gastrointestinal absorption, ability to penetrate the blood-brain barrier, non-P-glycoprotein nature, and antiparkinsonian effects.Nicotine plays crucial roles in the pathophysiology of PD. Further work is needed to evaluate the impact of nicotine on non-motor symptoms. We aimed to elucidate the molecular processes involved in how nicotine affects PD. Toxicogenomic, molecular mechanisms, physicochemical properties, pharmacokinetic profile, and biological activity were analysed. We found that the therapeutic potential of nicotine in PD may be attributed to its ability to modulate the expression of 38 genes, especially GAPDH, TNF, IL6, and BDNF. The molecular mechanisms underlying the protective effects of nicotine against PD involve several pathways, including the ‘Parkinson’s disease pathway’, ‘the selenium micronutrient network’, ‘the oxidative stress response’, ‘dopamine binding’, ‘Parkinsonian disorders’, and ‘Lewy body disease’. miRNAs like hsa-miRNA-203a-3p and miRNA-26b-5p and transcription factors like HNF4, MAPK3, and EVI1 explained how nicotine protects neurons from PD. An assessment was also carried out on drug candidates (polaprezinc) and miRNA sponges (hsa-miR-181a-5p, hsa-miR-124-3p, hsa-miR-1-3p) that may possess the capability to synergize the effects of nicotine. Nicotine’s physicochemical properties, pharmacokinetic profile, and biological activity are conducive to its favourable attributes in the context of PD, including high gastrointestinal absorption, ability to penetrate the blood-brain barrier, non-P-glycoprotein nature, and antiparkinsonian effects. Nicotine plays crucial roles in the pathophysiology of PD. Further work is needed to evaluate the impact of nicotine on non-motor symptoms.

本研究旨在阐明尼古丁影响帕金森病（Parkinson's Disease，PD）的相关分子过程。本研究对毒理基因组学（toxicogenomics）、分子机制、理化性质、药代动力学特征及生物学活性进行了分析。研究发现，尼古丁用于PD治疗的潜在价值，可归因于其能够调控38个基因的表达，尤其是GAPDH、TNF、IL6及BDNF。尼古丁抗PD保护作用的潜在分子机制涉及多条信号通路，包括"帕金森病通路""硒微量营养素网络""氧化应激应答""多巴胺结合""帕金森综合征"以及"路易体病"。诸如hsa-miRNA-203a-3p与miRNA-26b-5p等微小RNA（microRNAs，miRNAs），以及HNF4、MAPK3、EVI1等转录因子，可阐释尼古丁保护神经元免受PD损伤的机制。本研究同时对可协同增强尼古丁作用的候选药物（聚普瑞锌（polaprezinc））以及miRNA海绵（miRNA sponges，hsa-miR-181a-5p、hsa-miR-124-3p、hsa-miR-1-3p）进行了评估。尼古丁的理化性质、药代动力学特征及生物学活性，有助于其在PD场景下展现优良特性，包括高胃肠道吸收率、可穿透血脑屏障（blood-brain barrier）、非P-糖蛋白（P-glycoprotein）底物特性以及抗帕金森病活性。尼古丁在PD的病理生理过程中发挥关键作用。未来仍需开展进一步研究，以评估尼古丁对PD非运动症状的影响。本研究旨在阐明尼古丁影响PD的相关分子过程。本研究对毒理基因组学、分子机制、理化性质、药代动力学特征及生物学活性进行了分析。研究发现，尼古丁用于PD治疗的潜在价值，可归因于其能够调控38个基因的表达，尤其是GAPDH、TNF、IL6及BDNF。尼古丁抗PD保护作用的潜在分子机制涉及多条信号通路，包括"帕金森病通路""硒微量营养素网络""氧化应激应答""多巴胺结合""帕金森综合征"以及"路易体病"。诸如hsa-miRNA-203a-3p与miRNA-26b-5p等微小RNA，以及HNF4、MAPK3、EVI1等转录因子，可阐释尼古丁保护神经元免受PD损伤的机制。本研究同时对可协同增强尼古丁作用的候选药物（聚普瑞锌）以及miRNA海绵（hsa-miR-181a-5p、hsa-miR-124-3p、hsa-miR-1-3p）进行了评估。尼古丁的理化性质、药代动力学特征及生物学活性，有助于其在PD场景下展现优良特性，包括高胃肠道吸收率、可穿透血脑屏障、非P-糖蛋白底物特性以及抗帕金森病活性。尼古丁在PD的病理生理过程中发挥关键作用。未来仍需开展进一步研究，以评估尼古丁对PD非运动症状的影响。