Okafor Michael, Faller Peter, Vitale Nicolas
Laboratory of Biometals and Biological Chemistry, Institut de Chimie (UMR 7177), Université de Strasbourg-CNRS, 4 Rue Blaise Pascal, 67000, Strasbourg, France.
Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, 67000, Strasbourg, France.
Transl Neurodegener. 2025 Aug 22;14(1):42. doi: 10.1186/s40035-025-00504-6.
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by progressive decline of cognitive functions, yet its underlying aetiology remains elusive. While amyloid-β (Aβ) and tau pathologies have been extensively studied, emerging evidence suggests that metal and especially copper dyshomeostasis may also play a crucial role in the pathogenesis of AD. This review explores the intricate relationship between copper and AD, shedding light on the multifaceted mechanisms through which copper dysregulation contributes to neurodegeneration. We delve into the impact of copper ions on Aβ aggregation, tau phosphorylation, and oxidative stress, providing a comprehensive overview of the molecular pathways involved. Furthermore, we discuss the interplay between different brain cell types and the impact Cu dysregulation may have on them. The therapeutic implications of targeting copper dysregulation for AD treatment are also addressed, emphasizing the potential of copper-modulating agents in ameliorating cognitive decline. In summary, this review discusses copper dyshomeostasis as a central player in the intricate tapestry of AD pathology, offering new insights and avenues for therapeutic interventions.
阿尔茨海默病(AD)是一种复杂的神经退行性疾病,其特征为认知功能进行性衰退,但其潜在病因仍不明确。虽然淀粉样β蛋白(Aβ)和tau蛋白病变已得到广泛研究,但新出现的证据表明,金属尤其是铜的稳态失衡可能在AD的发病机制中也起着关键作用。本综述探讨了铜与AD之间的复杂关系,揭示了铜调节异常导致神经退行性变的多方面机制。我们深入研究了铜离子对Aβ聚集、tau蛋白磷酸化和氧化应激的影响,全面概述了相关分子途径。此外,我们还讨论了不同脑细胞类型之间的相互作用以及铜调节异常可能对它们产生的影响。还探讨了针对铜调节异常进行AD治疗的潜在意义,强调了铜调节药物在改善认知衰退方面的潜力。总之,本综述将铜稳态失衡视为AD病理复杂网络中的核心因素,为治疗干预提供了新的见解和途径。