Tortajada-Pérez Julia, Carranza Andrea Del Valle, Trujillo-Del Río Cristina, Collado-Pérez Mar, Millán José María, García-García Gema, Vázquez-Manrique Rafael Pascual
Laboratory of Molecular, Cellular and Genomic Biomedicine, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Joint Unit for Rare Diseases IIS La Fe-CIPF, 46026 Valencia, Spain.
Antioxidants (Basel). 2025 Jan 10;14(1):78. doi: 10.3390/antiox14010078.
Lipid metabolism plays a critical role in maintaining cellular integrity, especially within the nervous system, where lipids support neuronal structure, function, and synaptic plasticity. However, this essential metabolic pathway is highly susceptible to oxidative stress, which can lead to lipid peroxidation, a damaging process induced by reactive oxygen species. Lipid peroxidation generates by-products that disrupt many cellular functions, with a strong impact on proteostasis. In this review, we explore the role of lipid oxidation in protein folding and its associated pathological implications, with a particular focus on findings in neurodegeneration from studies, an animal model that remains underutilized. Additionally, we highlight the effectiveness of different methodologies applied in this nematode to deepen our understanding of this intricate process. In the nervous system of any animal, including mammals and invertebrates, lipid oxidation can disturb the delicate balance of cellular homeostasis, leading to oxidative stress, the build-up of toxic by-products, and protein misfolding, key factors in neurodegenerative diseases. This disruption contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's, or Huntington's disease. The findings from studies offer valuable insights into these complex processes and highlight potential avenues for developing targeted therapies to mitigate neurodegenerative disease progression.
脂质代谢在维持细胞完整性方面起着关键作用，尤其是在神经系统中，脂质支持神经元的结构、功能和突触可塑性。然而，这一重要的代谢途径极易受到氧化应激的影响，氧化应激会导致脂质过氧化，这是一种由活性氧引起的破坏性过程。脂质过氧化会产生破坏许多细胞功能的副产物，对蛋白质稳态有强烈影响。在这篇综述中，我们探讨了脂质氧化在蛋白质折叠中的作用及其相关的病理影响，特别关注秀丽隐杆线虫研究中的发现，该动物模型的利用程度仍然不足。此外，我们强调了在这种线虫中应用的不同方法的有效性，以加深我们对这一复杂过程的理解。在包括哺乳动物和无脊椎动物在内的任何动物的神经系统中，脂质氧化都会扰乱细胞内稳态的微妙平衡，导致氧化应激、有毒副产物的积累和蛋白质错误折叠，而这些都是神经退行性疾病的关键因素。这种破坏促成了阿尔茨海默病、帕金森病或亨廷顿病等神经退行性疾病的发病机制。秀丽隐杆线虫研究的结果为这些复杂过程提供了有价值的见解，并突出了开发靶向治疗以减轻神经退行性疾病进展的潜在途径。
