Parkinson's disease (PD) relates to defective mitochondrial quality control in the dopaminergic motor network. Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset, pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra (SNpc). In a reciprocal manner, LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation. Pharmacological intervention in these disease-modifying pathways may facilitate the development of novel PD therapeutics, despite the current lack of an established drug evaluation model. As such, we reviewed the feasibility of employing the versatile global Pink1 knockout (KO) rat model as a self-sufficient, spontaneous PD model for investigating both disease etiology and drug pharmacology. These rats retain clinical features encompassing basal mitophagic flux changes with PD progression. We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.
帕金森病（PD）是一种常见的神经退行性疾病，与多巴胺能神经元中线粒体功能调控紊乱有关。遗传学研究表示PINK1 和Parkin的基因突变与帕金森病有关，而这两种蛋白被认为是通过线粒体自噬和炎症调控来保护中脑黑质区域的神经元退变死亡。同样，LRRK2通过调节线粒体功能障碍，氧化应激及泛素蛋白酶体系，参与到PINK1/Parkin介导的线粒体自噬调控网络中。因此，针对病变中信号调控通路靶点开发药物，可更有效的针对帕金森病的异质性实现组合疗法。虽然目前并没有完美的帕金森研究模型，但使用相关基因敲除动物模型对研究该疾病具体作用机制和治疗手段具有重要意义。该文总结了目前有关的Pink1基因敲除（KO）模型研究现状，讨论了Pink1敲除小鼠和大鼠模型与PD患者临床差异。该文指出，Pink1基因敲除大鼠作为一种自发的PD模型，不仅表现出帕金森病的临床多样性特征，其线粒体自噬水平和炎症反应也会随着帕金森病情发展发生变化，为进一步研究PD发病机理和开发治疗药物提供模型参考。.
Keywords: Genetic model; Inflammatory response; Mitophagy; Parkinson’s disease; Pink1 KO rats.