Wang Congmin, Hei Yu, Liu Yu, Bajpai Akhilesh Kumar, Li Yuhe, Guan Yawen, Xu Fuyi, Yao Cuifang
School of Pharmacy, Binzhou Medical University, Yantai, China.
Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai, China.
Front Neurosci. 2024 Jul 16;18:1381889. doi: 10.3389/fnins.2024.1381889. eCollection 2024.
As a dietary strategy, methionine restriction has been reported to promote longevity and regulate metabolic disorders. However, the role and possible regulatory mechanisms underlying methionine in neurodegenerative diseases such as Alzheimer's disease (AD), remain unexplored. This study utilized the data from BXD recombinant inbred (RI) mice to establish a correlation between the AD phenotype in mice and methionine level. Gene enrichment analysis indicated that the genes associated with the concentration of methionine in the midbrain are involved in the dopaminergic synaptic signaling pathway. Protein interaction network analysis revealed that glycogen synthase kinase 3 beta (GSK-3β) was a key regulator of the dopaminergic synaptic pathway and its expression level was significantly correlated with the AD phenotype. Finally, experiments demonstrated that methionine deprivation could reduce the expression of Aβ and phosphorylated Tau, suggesting that lowering methionine levels in humans may be a preventive or therapeutic strategy for AD. In conclusion, our findings support that methionine is a high risk factor for AD. These findings predict potential regulatory network, theoretically supporting methionine restriction to prevent AD.
作为一种饮食策略，据报道蛋氨酸限制可促进长寿并调节代谢紊乱。然而，蛋氨酸在诸如阿尔茨海默病（AD）等神经退行性疾病中的作用及潜在调控机制仍未得到探索。本研究利用BXD重组近交（RI）小鼠的数据，建立小鼠AD表型与蛋氨酸水平之间的相关性。基因富集分析表明，与中脑蛋氨酸浓度相关的基因参与多巴胺能突触信号通路。蛋白质相互作用网络分析显示，糖原合酶激酶3β（GSK - 3β）是多巴胺能突触通路的关键调节因子，其表达水平与AD表型显著相关。最后，实验证明蛋氨酸剥夺可降低Aβ和磷酸化Tau的表达，这表明降低人类体内的蛋氨酸水平可能是预防或治疗AD的一种策略。总之，我们的研究结果支持蛋氨酸是AD的高风险因素。这些发现预测了潜在的调控网络，从理论上支持蛋氨酸限制以预防AD。
