Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on neuronal homeostasis and the immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we describ approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We also highlight the possible use of clinical and non-clinical drugs to modulate the sphingolipid pathway and sphingolipid-related biological cascades.

中文翻译：

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阿尔茨海默病中的鞘脂，我们如何针对它们？

大脑中鞘脂及其代谢物水平的改变，以及对神经元稳态和免疫系统的相关下游影响，为了解神经退行性疾病的机制和制定新的干预策略提供了框架。在这篇综述中，我们将讨论： 作为第二信使的鞘脂代谢物；和导致阿尔茨海默病 (AD) 病理生理学的途径的功能异常。关注鞘脂途径神经酰胺的核心产物，我们描述了药物降低大脑中神经酰胺水平的方法，并讨论了鞘脂途径如何代表开发 AD 新干预策略的新框架。