Sphingoid Base Diversity

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Atherosclerosis Pub Date : 2025-02-01 DOI:10.1016/j.atherosclerosis.2024.119091

Thorsten Hornemann

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Abstract

Sphingolipids (SL) are crucial components of cellular membranes and play pivotal roles in various biological processes, including cell growth, differentiation, apoptosis, and stress responses. All SL contain a sphingoid base (SPB) backbone which is the shared and class-defining element. SPBs are heterogeneous in length and structure. This review summarizes our current understanding on minor SPBs and the role of the serine palmitoyltransferase (SPT) in particular of its subunits SPTLC3 and SPTSSA/B in forming a spectrum of structurally and metabolically distinct SPBs.

Some minor SPBs, such as 1-deoxysphingolipids (1-deoxySL) are neurotoxic and associated with neurological disorders such as hereditary sensory neuropathy type 1 (HSAN1) and diabetic neuropathy.

Furthermore, the review discusses the pathological implications of atypical SPBs in cardiometabolic conditions such as obesity, type 2 diabetes or cardiomyopathy, where the induction of the SPTLC3 subunit alters the SPB profile and contributes to disease progression.

Understanding these, often neglected aspects of the sphingolipid metabolism provides potential therapeutic targets for metabolic and neurodegenerative diseases, emphasizing the need for continued research in this area.

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鞘基多样性。

鞘脂（Sphingolipids， SL）是细胞膜的重要组成部分，在细胞生长、分化、凋亡和应激反应等多种生物过程中发挥着关键作用。所有SL都包含一个SPB骨干，SPB骨干是共享的类定义元素。spb在长度和结构上是不均匀的。本文综述了目前我们对小SPBs的认识，以及丝氨酸棕榈酰转移酶（SPT），特别是其亚基SPTLC3和SPTSSA/B在形成结构和代谢不同的SPBs谱中的作用。一些较小的SPBs，如1-脱氧鞘脂（1- deoxysl）具有神经毒性，与遗传性1型感觉神经病变（HSAN1）和糖尿病性神经病变等神经系统疾病有关。此外，该综述还讨论了非典型SPB在心脏代谢疾病（如肥胖、2型糖尿病或心肌病）中的病理意义，在这些疾病中，SPTLC3亚基的诱导改变了SPB的特征并促进了疾病的进展。了解这些经常被忽视的鞘脂代谢方面为代谢性和神经退行性疾病提供了潜在的治疗靶点，强调了在这一领域继续研究的必要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.