Neurosciences Division, Cell Physiology Institute, National Autonomous University of Mexico, Coyoacan, Mexico City 04510, Mexico.
Regenerative Medicine Laboratory, Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Coyoacan, Mexico City 04510, Mexico.
Cells. 2022 Oct 31;11(21):3445. doi: 10.3390/cells11213445.
The complexity and overall burden of Parkinson's disease (PD) require new pharmacological approaches to counteract the symptomatology while reducing the progressive neurodegeneration of affected dopaminergic neurons. Since the pathophysiological signature of PD is characterized by the loss of physiological levels of dopamine (DA) and the misfolding and aggregation of the alpha-synuclein (α-syn) protein, new proposals seek to restore the lost DA and inhibit the progressive damage derived from pathological α-syn and its impact in terms of oxidative stress. In this line, nanomedicine (the medical application of nanotechnology) has achieved significant advances in the development of nanocarriers capable of transporting and delivering basal state DA in a controlled manner in the tissues of interest, as well as highly selective catalytic nanostructures with enzyme-like properties for the elimination of reactive oxygen species (responsible for oxidative stress) and the proteolysis of misfolded proteins. Although some of these proposals remain in their early stages, the deepening of our knowledge concerning the pathological processes of PD and the advances in nanomedicine could endow for the development of potential treatments for this still incurable condition. Therefore, in this paper, we offer: (i) a brief summary of the most recent findings concerning the physiology of motor regulation and (ii) the molecular neuropathological processes associated with PD, together with (iii) a recapitulation of the current progress in controlled DA release by nanocarriers and (iv) the design of nanozymes, catalytic nanostructures with oxidoreductase-, chaperon, and protease-like properties. Finally, we conclude by describing the prospects and knowledge gaps to overcome and consider as research into nanotherapies for PD continues, especially when clinical translations take place.
帕金森病（PD）的复杂性和总体负担需要新的药物治疗方法来对抗症状，同时减少受影响的多巴胺能神经元的进行性神经退行性变。由于 PD 的病理生理特征是多巴胺（DA）生理水平的丧失以及α-突触核蛋白（α-syn）的错误折叠和聚集，新的方案旨在恢复失去的 DA 并抑制源自病理性α-syn 的进行性损伤及其在氧化应激方面的影响。在这方面，纳米医学（纳米技术在医学中的应用）在开发能够以受控方式在感兴趣的组织中运输和递送达基础状态 DA 的纳米载体方面取得了重大进展，以及具有酶样特性的高度选择性催化纳米结构，用于消除活性氧物质（负责氧化应激）和错误折叠蛋白质的蛋白水解。尽管其中一些方案仍处于早期阶段，但我们对 PD 的病理过程的深入了解和纳米医学的进步可能为这种仍然无法治愈的疾病的潜在治疗方法的开发提供了可能。因此，在本文中，我们提供了：（i）关于运动调节生理学的最新发现的简要总结，（ii）与 PD 相关的分子神经病理学过程，以及（iii）纳米载体控制 DA 释放的当前进展的概述，以及（iv）纳米酶的设计，具有氧化还原酶、伴侣和蛋白酶样特性的催化纳米结构。最后，我们通过描述前景和知识差距来结束，这些差距需要克服并考虑作为 PD 的纳米治疗研究的继续，特别是当临床转化发生时。
