Valenzuela-Ahumada Luis Armando, Mercado-Gómez Octavio Fabián, Viveros-Contreras Rubi, Guevara-Guzmán Rosalinda, Camacho-Morales Alberto
Department of Biochemistry, College of Medicine, Universidad Autónoma de Nuevo León, Monterrey, Mexico.
Department of Physiology, College of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Front Neurosci. 2025 Jun 4;19:1602149. doi: 10.3389/fnins.2025.1602149. eCollection 2025.
Neurodegenerative diseases affect up to 349.2 million individuals worldwide. Preclinical and clinical advances have documented that altered energy homeostasis and mitochondria dysfunction is a hallmark of neurological disorders. Diet-derived ceramides species might target and disrupt mitochondria function leading to defective energy balance and neurodegeneration. Ceramides as bioactive lipid species affect mitochondria function by several mechanism including changes in membrane chemical composition, inhibition of the respiratory chain, ROS overproduction and oxidative stress, and also by activating mitophagy. Promising avenues of intervention has documented that intermittent fasting (IF) is able to benefit and set proper energy metabolism. IF is an eating protocol that involves alternating periods of fasting with periods of eating which modulate ceramide metabolism and mitochondria function in neurons. This review will address the detrimental effect of ceramides on mitochondria membrane composition, respiratory chain, ROS dynamics and mitophagy in brain contributing to neurodegeneration. We will focus on effect of IF on ceramide metabolism as a potential avenue to improve mitochondria function and prevention of neurodegeneration.
神经退行性疾病影响着全球多达3.492亿人。临床前和临床研究进展已证明，能量稳态改变和线粒体功能障碍是神经疾病的一个标志。饮食来源的神经酰胺可能靶向并破坏线粒体功能，导致能量平衡缺陷和神经退行性变。作为生物活性脂质的神经酰胺通过多种机制影响线粒体功能，包括膜化学成分的变化、呼吸链的抑制、活性氧的过量产生和氧化应激，还通过激活线粒体自噬。有前景的干预途径已证明，间歇性禁食（IF）能够有益并建立适当的能量代谢。IF是一种饮食方案，包括禁食期和进食期交替，可调节神经元中的神经酰胺代谢和线粒体功能。本综述将探讨神经酰胺对脑中线粒体膜组成、呼吸链、活性氧动态和线粒体自噬的有害影响，这些影响会导致神经退行性变。我们将关注间歇性禁食对神经酰胺代谢的影响，这是改善线粒体功能和预防神经退行性变的一个潜在途径。
