Schepers Jana, Löser Timo, Behl Christian
The Autophagy Lab, Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Front Mol Biosci. 2024 Aug 12;11:1455817. doi: 10.3389/fmolb.2024.1455817. eCollection 2024.
Aggregation of alpha-Synuclein (αSyn) has been connected to several neurodegenerative diseases, such as Parkinson's disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), that are collected under the umbrella term The membrane binding abilities of αSyn to negatively charged phospholipids have been well described and are connected to putative physiological functions of αSyn. Consequently, αSyn-related neurodegeneration has been increasingly connected to changes in lipid metabolism and membrane lipid composition. Indeed, αSyn aggregation has been shown to be triggered by the presence of membranes , and some genetic risk factors for PD and DLB are associated with genes coding for proteins directly involved in lipid metabolism. At the same time, αSyn aggregation itself can cause alterations of cellular lipid composition and brain samples of patients also show altered lipid compositions. Thus, it is likely that there is a reciprocal influence between cellular lipid composition and αSyn aggregation, which can be further affected by environmental or genetic factors and ageing. Little is known about lipid changes during physiological ageing and regional differences of the lipid composition of the aged brain. In this review, we aim to summarise our current understanding of lipid changes in connection to αSyn and discuss open questions that need to be answered to further our knowledge of αSyn related neurodegeneration.
α-突触核蛋白（αSyn）的聚集与多种神经退行性疾病相关，如帕金森病（PD）、路易体痴呆（DLB）和多系统萎缩（MSA），这些疾病统称为α-突触核蛋白病。αSyn与带负电荷磷脂的膜结合能力已得到充分描述，并与αSyn的假定生理功能相关。因此，αSyn相关的神经退行性变越来越多地与脂质代谢和膜脂质组成的变化联系在一起。事实上，αSyn聚集已被证明是由膜的存在引发的，并且PD和DLB的一些遗传风险因素与直接参与脂质代谢的蛋白质编码基因有关。同时，αSyn聚集本身可导致细胞脂质组成的改变，患者的脑样本也显示脂质组成发生改变。因此，细胞脂质组成与αSyn聚集之间可能存在相互影响，这可能会受到环境或遗传因素以及衰老的进一步影响。关于生理性衰老过程中的脂质变化以及老年大脑脂质组成的区域差异，人们知之甚少。在这篇综述中，我们旨在总结我们目前对与αSyn相关的脂质变化的理解，并讨论为进一步了解αSyn相关神经退行性变而需要回答的开放性问题。
