Fumagalli F, Racagni G, Riva M A
Department of Pharmacological Sciences, Center of Neuropharmacology, Milan, Italy.
Pharmacogenomics J. 2006 Mar-Apr;6(2):95-104. doi: 10.1038/sj.tpj.6500360.
Parkinson's disease (PD) is a chronic, neurodegenerative disease with a 1% incidence in the population over 55 years of age. Movement impairments represent undoubtedly the hallmark of the disorder; however, extensive evidence implicates cognitive deficits as concomitant peculiar features. Brain-derived neurotrophic factor (BDNF) colocalizes with dopamine neurons in the substantia nigra, where dopaminergic cell bodies are located, and it has recently garnered attention as a molecule crucial for cognition, a function that is also compromised in PD patients. Thus, due to its colocalization with dopaminergic neurons and its role in cognition, BDNF might possess a dual role in PD, both as a neuroprotective molecule, since its inhibition leads to loss of nigral dopaminergic neurons, and as a neuromodulator, as its enhanced expression ameliorates cognitive processes. In this review, we discuss the mechanism of action of established as well as novel drugs for PD with a particular emphasis to those interfering with BDNF biosynthesis.
帕金森病（PD）是一种慢性神经退行性疾病，在55岁以上人群中的发病率为1%。运动障碍无疑是该疾病的标志；然而，大量证据表明认知缺陷是伴随出现的特殊特征。脑源性神经营养因子（BDNF）与多巴胺能神经元在黑质中共定位，黑质是多巴胺能细胞体所在的位置，最近它作为一种对认知至关重要的分子受到关注，而在帕金森病患者中这种功能也受到损害。因此，由于其与多巴胺能神经元的共定位及其在认知中的作用，BDNF在帕金森病中可能具有双重作用，既是一种神经保护分子，因为其抑制会导致黑质多巴胺能神经元丢失，又是一种神经调节剂，因为其表达增强可改善认知过程。在这篇综述中，我们讨论了已有的以及新型帕金森病药物的作用机制，特别强调了那些干扰BDNF生物合成的药物。
