神经细胞斑中的神经酰胺和神经鞘磷脂酶。

Ceramides and sphingomyelinases in senile plaques.

机构信息

Laboratoire de Neuropathologie Escourolle, Hôpital de la Salpêtrière, AP-HP, Paris, France; Centre de recherche de l'ICM, UPMC, INSERM UMR S 975, CNRS UMR 7225, France.

Chimie-Toxicologie Analytique et Cellulaire, EA 4463, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, PRES Sorbonne Paris Cité, France; Division Métabolisme, Technologie Servier, Orléans, France.

出版信息

Neurobiol Dis. 2014 May;65:193-201. doi: 10.1016/j.nbd.2014.01.010. Epub 2014 Jan 28.

DOI:10.1016/j.nbd.2014.01.010

PMID:24486621

Abstract

The senile plaque is a hallmark lesion of Alzheimer disease (AD). We compared, without a priori, the lipidome of the senile plaques and of the adjacent plaque-free neuropil. The analysis by liquid chromatography coupled with electrospray ionization mass spectrometry revealed that laser microdissected senile plaques were enriched in saturated ceramides Cer(d18:1/18:0) and Cer(d18:1/20:0) by 33 and 78% respectively with respect to the surrounding neuropil. This accumulation of ceramides was not explained by their affinity for Aβ deposits: no interaction between ceramide-liposomes and Aβ fibrils was observed in vitro by surface plasmon resonance and fluorescent ceramide-liposomes showed no affinity for the senile plaques in AD brain tissue. Accumulation of ceramides could be, at least partially, the result of a local production by acid and neutral sphingomyelinases that we found to be present in the corona of the senile plaques.

摘要

老年斑是阿尔茨海默病 (AD) 的标志性病变。我们在没有先验知识的情况下比较了老年斑和相邻无斑神经突的脂质组。通过液相色谱-电喷雾电离质谱分析显示，与周围神经突相比，激光微切割的老年斑中饱和神经酰胺 Cer(d18:1/18:0) 和 Cer(d18:1/20:0) 分别富集了 33%和 78%。这种神经酰胺的积累不能用它们与 Aβ 沉积物的亲和力来解释：在体外通过表面等离子体共振观察到神经酰胺-脂质体与 Aβ 原纤维之间没有相互作用，荧光神经酰胺-脂质体对 AD 脑组织中的老年斑没有亲和力。神经酰胺的积累至少部分可能是由于酸性和中性鞘磷脂酶的局部产生所致，我们发现这些酶存在于老年斑的冠状物中。