Gutierrez-Cuesta Javier, Sureda Francesc X, Romeu Marta, Canudas Anna M, Caballero Beatriz, Coto-Montes Ana, Camins Antoni, Pallàs Mercè
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia and Institut de Biomedicina, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
J Pineal Res. 2007 Apr;42(4):394-402. doi: 10.1111/j.1600-079X.2007.00433.x.
Certain effects of melatonin on senescence were investigated. The experimental model used was 10-month-old senescence-accelerated mouse prone 8 (SAMP8). The mice in the experiment were administered melatonin (10 mg/kg) from the age of 1 month. Results showed that chronic administration of melatonin decreased cell loss in the cerebral cortex and reduced oxidative damage in protein and lipids. There are several studies suggesting that the activation of the cdk5/p35 pathway at its cleavage to cdk5/p25 may play a role in hyperphosphorylation of tau during aging and neurodegenerative diseases. Melatonin not only reduced the cerebral aging disturbances, but also prevented tau hyperphosphorylation present in the experimental model used in this study. Melatonin reduced cdk5 expression, as well as the cleavage of p35 to p25. The other tau kinase studied, GSK3beta, showed a reduction in this activity in comparison with SAMP8 nontreated SAMP8. These data indicate that melatonin possesses neuroprotective properties against cerebral damage gated to senescence. Moreover, these data suggest that the cdk5/GSKbeta signaling cascade has a potential role as a target for neurodegenerative diseases related to aging.
研究了褪黑素对衰老的某些影响。所使用的实验模型是10月龄的衰老加速易感性8型小鼠（SAMP8）。实验中的小鼠从1月龄开始给予褪黑素（10 mg/kg）。结果表明，长期给予褪黑素可减少大脑皮质中的细胞损失，并减少蛋白质和脂质的氧化损伤。有多项研究表明，cdk5/p35途径在其裂解为cdk5/p25时的激活可能在衰老和神经退行性疾病期间tau蛋白的过度磷酸化中起作用。褪黑素不仅减少了大脑衰老紊乱，还防止了本研究中使用的实验模型中存在的tau蛋白过度磷酸化。褪黑素降低了cdk5的表达以及p35裂解为p25。所研究的另一种tau激酶GSK3β与未处理的SAMP8相比，其活性降低。这些数据表明，褪黑素具有针对与衰老相关的脑损伤的神经保护特性。此外，这些数据表明cdk5/GSKβ信号级联作为与衰老相关的神经退行性疾病的靶点具有潜在作用。
