Yoo Jeasang, Han Jiyeon, Lim Mi Hee
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea
Department of Applied Chemistry, University of Seoul Seoul 02504 Republic of Korea
RSC Chem Biol. 2023 Jun 27;4(8):548-563. doi: 10.1039/d3cb00052d. eCollection 2023 Aug 3.
Neurodegeneration is characterized by a disturbance in neurotransmitter-mediated signaling pathways. Recent studies have highlighted the significant role of transition metal ions, including Cu(i/ii), Zn(ii), and Fe(ii/iii), in neurotransmission, thereby making the coordination chemistry of neurotransmitters a growing field of interest in understanding signal dysfunction. This review outlines the physiological functions of transition metal ions and neurotransmitters, with the metal-binding properties of small molecule-based neurotransmitters and neuropeptides. Additionally, we discuss the structural and conformational changes of neurotransmitters induced by redox-active metal ions, such as Cu(i/ii) and Fe(ii/iii), and briefly describe the outcomes arising from their oxidation, polymerization, and aggregation. These observations have important implications for neurodegeneration and emphasize the need for further research to develop potential therapeutic strategies.
神经退行性变的特征是神经递质介导的信号通路紊乱。最近的研究强调了过渡金属离子,包括铜(Ⅰ/Ⅱ)、锌(Ⅱ)和铁(Ⅱ/Ⅲ)在神经传递中的重要作用,从而使神经递质的配位化学成为理解信号功能障碍中一个日益受到关注的领域。本综述概述了过渡金属离子和神经递质的生理功能,以及基于小分子的神经递质和神经肽的金属结合特性。此外,我们讨论了氧化还原活性金属离子,如铜(Ⅰ/Ⅱ)和铁(Ⅱ/Ⅲ)诱导的神经递质的结构和构象变化,并简要描述了它们氧化、聚合和聚集所产生的结果。这些观察结果对神经退行性变具有重要意义,并强调需要进一步研究以开发潜在的治疗策略。