Bacchella Chiara, Capucciati Andrea, Monzani Enrico
Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy.
Fondazione Grigioni per il Morbo di Parkinson, Via Gianfranco Zuretti 35, 20125 Milano, Italy.
Antioxidants (Basel). 2025 Mar 15;14(3):347. doi: 10.3390/antiox14030347.
Neurodegenerative disorders are one of the main public health problems worldwide and, for this reason, they have attracted the attention of several researchers who aim to better understand the molecular processes linked to the etiology of these disorders, including Alzheimer's and Parkinson's diseases. In this review, we describe both the beneficial and toxic effect of norepinephrine (NE) and its connected ROS/metal-mediated pathways, which end in neuromelanin (NM) formation and protein aggregation. In particular, we emphasize the importance of stabilizing the delicate homeostatic balance that regulates () the metal/ROS-promoted oxidation of catecholamines, as NE, and () the generation of oxidative by-products capable of covalently and non-covalently modifying neuroproteins, thus altering their stability and their oligomerization; these processes may end in () the incorporation of protein conjugates into vesicles, which then evolve into neuromelanin (NM) organelles. In general, we aim to provide an up-to-date overview of the challenges and controversies emerging from the current literature to delineate a direction for future research.
神经退行性疾病是全球主要的公共卫生问题之一，因此，它们吸引了众多研究人员的关注，这些研究人员旨在更好地理解与这些疾病病因相关的分子过程，包括阿尔茨海默病和帕金森病。在这篇综述中，我们描述了去甲肾上腺素（NE）的有益和毒性作用及其相关的ROS/金属介导途径，这些途径最终导致神经黑色素（NM）的形成和蛋白质聚集。特别是，我们强调了稳定调节以下方面的微妙体内平衡的重要性：（1）金属/ROS促进的儿茶酚胺（如NE）氧化；（2）能够共价和非共价修饰神经蛋白从而改变其稳定性和寡聚化的氧化副产物的产生；这些过程可能最终导致（3）蛋白质结合物掺入囊泡，然后囊泡演变成神经黑色素（NM）细胞器。总体而言，我们旨在提供当前文献中出现的挑战和争议的最新概述，为未来研究指明方向。
