Pawłowska Marta, Kruszka Joanna, Porzych Marta, Garbarek Jakub, Nuszkiewicz Jarosław
Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland.
Student Research Club of Medical Biology and Biochemistry, Department of Medical Biology and Biochemistry, Faculty of Medicine, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 24 Karłowicza St., 85-092 Bydgoszcz, Poland.
Metabolites. 2025 Jul 31;15(8):508. doi: 10.3390/metabo15080508.
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are characterized by progressive neuronal loss and share key pathological features such as oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Recent research has highlighted the potential of ketogenic metabolism, particularly the use of ketone bodies like β-hydroxybutyrate, as a therapeutic approach targeting these shared mechanisms. This review provides a comprehensive synthesis of current knowledge on the neuroprotective effects of ketogenic interventions, including both dietary strategies and exogenous ketone supplementation. We discuss how ketone bodies improve mitochondrial function, reduce reactive oxygen species, modulate inflammatory pathways, and influence neurotransmission and synaptic plasticity. Additionally, we examine experimental and clinical evidence supporting the application of ketogenic therapies in neurodegenerative diseases, highlighting disease-specific findings, benefits, and limitations. While preclinical data are robust and suggest meaningful therapeutic potential, clinical studies remain limited and heterogeneous, with challenges related to adherence, safety, and patient selection. The review also addresses the translational relevance of ketogenic strategies, considering their feasibility, combination with other therapies, and the need for personalized approaches based on genetic and metabolic profiles. By critically evaluating existing data, this article aims to clarify the mechanisms through which ketogenic metabolism may exert neuroprotective effects and to outline future directions for research and clinical application in the context of neurodegenerative disorders.
神经退行性疾病，包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症，其特征是神经元进行性丧失，并具有氧化应激、线粒体功能障碍和慢性神经炎症等关键病理特征。最近的研究强调了生酮代谢的潜力，特别是使用β-羟基丁酸等酮体作为针对这些共同机制的治疗方法。本综述全面综合了目前关于生酮干预神经保护作用的知识，包括饮食策略和外源性酮补充。我们讨论了酮体如何改善线粒体功能、减少活性氧、调节炎症途径以及影响神经传递和突触可塑性。此外，我们研究了支持生酮疗法在神经退行性疾病中应用的实验和临床证据，突出了疾病特异性的发现、益处和局限性。虽然临床前数据确凿并显示出有意义的治疗潜力，但临床研究仍然有限且参差不齐，存在与依从性、安全性和患者选择相关的挑战。该综述还讨论了生酮策略的转化相关性，考虑了其可行性、与其他疗法的联合使用以及基于遗传和代谢特征的个性化方法的必要性。通过批判性地评估现有数据，本文旨在阐明生酮代谢可能发挥神经保护作用的机制，并概述神经退行性疾病背景下未来的研究和临床应用方向。
