Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Neurochem Res. 2011 Feb;36(2):215-22. doi: 10.1007/s11064-010-0305-1. Epub 2010 Nov 4.
Parkinson's disease (PD) is characterized by a progressive neurodegeneration in the substantia nigra and a striatal dopamine decrease. Striatal extracellular adenosine and ATP modulate the dopaminergic neurotransmission whereas guanosine has a protective role in the brain. Therefore, the regulation of their levels by enzymatic activity may be relevant to the clinical feature of PD. Here it was evaluated the extracellular nucleotide hydrolysis from striatal slices 4 weeks after a unilateral infusion with 6-OHDA into the medial forebrain bundle. This infusion increased ADP, AMP, and GTP hydrolysis by 15, 25, and 41%, respectively, and decreased GDP hydrolysis by 60%. There was no change in NTPDases1, 2, 3, 5, 6, and 5'-nucleotidase transcription. Dopamine depletion changes nucleotide hydrolysis and, therefore, alters the regulation of striatal nucleotide levels. These changes observed in 6-OHDA-lesioned animals may contribute to the symptoms observed in the model and provide evidence to indicate that extracellular purine hydrolysis is a key factor in understanding PD, giving hints for new therapies.
帕金森病（PD）的特征是黑质中进行性神经退行性变和纹状体多巴胺减少。纹状体细胞外腺苷和 ATP 调节多巴胺能神经传递，而鸟苷在大脑中具有保护作用。因此，酶活性对其水平的调节可能与 PD 的临床特征相关。此处评估了单侧内侧前脑束内注射 6-OHDA 4 周后纹状体切片的细胞外核苷酸水解。该注射使 ADP、AMP 和 GTP 水解分别增加了 15%、25%和 41%，并使 GDP 水解减少了 60%。NTPDases1、2、3、5、6 和 5'-核苷酸酶转录没有变化。多巴胺耗竭改变核苷酸水解，从而改变纹状体核苷酸水平的调节。在 6-OHDA 损伤动物中观察到的这些变化可能有助于该模型中观察到的症状，并提供证据表明细胞外嘌呤水解是理解 PD 的关键因素，为新疗法提供了线索。
