Chowdhury Md Riad, Jin Hee Kyung, Bae Jae-Sung
KNU Alzheimer's Disease Research Institute, Kyungpook National University, Daegu 41566, Korea.
Department of Physiology, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Biomedicines. 2022 Aug 12;10(8):1956. doi: 10.3390/biomedicines10081956.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, and is associated with several pathophysiological features, including cellular dysfunction, failure of neurotransmission, cognitive impairment, cell death, and other clinical consequences. Advanced research on the pathogenesis of AD has elucidated a mechanistic framework and revealed many therapeutic possibilities. Among the mechanisms, sphingolipids are mentioned as distinctive mediators to be associated with the pathology of AD. Reportedly, alteration in the metabolism of sphingolipids and their metabolites result in the dysfunction of mitochondria, autophagy, amyloid beta regulation, and neuronal homeostasis, which exacerbates AD progression. Considering the importance of sphingolipids, in this review, we discuss the role of ceramide, a bioactive sphingolipid metabolite, in the progression and pathogenesis of AD. Herein, we describe the ceramide synthesis pathway and its involvement in the dysregulation of homeostasis, which eventually leads to AD. Furthermore, this review references different therapeutics proposed to modulate the ceramide pathway to maintain ceramide levels and prevent the disease progression.
阿尔茨海默病（AD）是最常见的神经退行性疾病，与多种病理生理特征相关，包括细胞功能障碍、神经传递失败、认知障碍、细胞死亡及其他临床后果。对AD发病机制的深入研究阐明了一个机制框架，并揭示了许多治疗可能性。在这些机制中，鞘脂被认为是与AD病理相关的独特介质。据报道，鞘脂及其代谢产物的代谢改变会导致线粒体功能障碍、自噬、β-淀粉样蛋白调节和神经元稳态失衡，从而加剧AD的进展。鉴于鞘脂的重要性，在本综述中，我们讨论了生物活性鞘脂代谢产物神经酰胺在AD进展和发病机制中的作用。在此，我们描述了神经酰胺合成途径及其在稳态失调中的作用，最终导致AD。此外，本综述还提及了为调节神经酰胺途径以维持神经酰胺水平和预防疾病进展而提出的不同治疗方法。
