Jankowski Marek
Zaklad Genetyki, Instytut Biologii Ogólnej i Molekularnej, Uniwersytet Mikołaja Kopernika w Toruniu.
Postepy Biochem. 2007;53(3):297-303.
Parkinson's disease is a neurodegenerative disorder characterized by a dramatic loss of dopaminergic neurons in the substantia nigra. Among the many pathogenic mechanisms thought to contribute to the demise of these cells in sporadic cases of PD, oxidative stress has taken center stage due to extensive experimental evidence showing that dopamine- or MPTP-derived reactive oxygen species and oxidized dopamine metabolites may trigger toxicity through mitochondrial inhibition or deleterious modifications of biomolecules. In familial forms of PD, however, the involvement of toxic protein aggregation (synuclein), impairment of ubiquitin-proteosome system (parkin. and loss of antioxidative properties (DJ-1) has gained attention. Recently, JNK pathway has come to light that could link malfunction of mutated DJ-1, parkin, PINK1 and alpha-synuclein to the oxidative stress-triggered apoptosis, finally ascribing a common pathogenic mechanism to both the sporadic and familial forms of PD.
帕金森病是一种神经退行性疾病，其特征是黑质中多巴胺能神经元显著丧失。在散发性帕金森病病例中，许多致病机制被认为与这些细胞的死亡有关，其中氧化应激由于大量实验证据而成为焦点，这些证据表明多巴胺或MPTP衍生的活性氧和氧化多巴胺代谢产物可能通过线粒体抑制或生物分子的有害修饰引发毒性。然而，在家族性帕金森病中，有毒蛋白质聚集（突触核蛋白）、泛素-蛋白酶体系统受损（帕金）和抗氧化特性丧失（DJ-1）的参与受到了关注。最近，JNK信号通路被发现，它可能将突变的DJ-1、帕金、PINK1和α-突触核蛋白的功能障碍与氧化应激引发的细胞凋亡联系起来，最终为散发性和家族性帕金森病形式赋予了共同的致病机制。
