Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Rome, Italy.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; IRCCS Mondino Foundation, Pavia, Italy.
Neurobiol Dis. 2022 Oct 15;173:105851. doi: 10.1016/j.nbd.2022.105851. Epub 2022 Aug 23.
Parkinson's disease (PD) is a multifactorial disorder involving a complex interplay between a variety of genetic and environmental factors. In this scenario, mitochondrial impairment and oxidative stress are widely accepted as crucial neuropathogenic mechanisms, as also evidenced by the identification of PD-associated genes that are directly involved in mitochondrial function. The concept of mitochondrial dysfunction is closely linked to that of synaptic dysfunction. Indeed, compelling evidence supports the role of mitochondria in synaptic transmission and plasticity, although many aspects have not yet been fully elucidated. Here, we will provide a brief overview of the most relevant evidence obtained in different neurotoxin-based and genetic rodent models of PD, focusing on mitochondrial impairment and synaptopathy, an early central event preceding overt nigrostriatal neurodegeneration. The identification of early deficits occurring in PD pathogenesis is crucial in view of the development of potential disease-modifying therapeutic strategies.
帕金森病（PD）是一种涉及多种遗传和环境因素复杂相互作用的多因素疾病。在这种情况下，线粒体损伤和氧化应激被广泛认为是关键的神经发病机制，这也得到了与线粒体功能直接相关的 PD 相关基因的鉴定的证实。线粒体功能障碍的概念与突触功能障碍密切相关。事实上，有确凿的证据支持线粒体在突触传递和可塑性中的作用，尽管许多方面尚未完全阐明。在这里，我们将简要概述在不同的神经毒素和遗传 PD 啮齿动物模型中获得的最相关证据，重点关注线粒体损伤和突触病，这是在明显的黑质纹状体神经退行性变之前发生的早期中枢事件。鉴于潜在的疾病修饰治疗策略的发展，确定在 PD 发病机制中发生的早期缺陷至关重要。
