磷脂重塑与帕金森病  被引量:1

Phospholipid remodeling and Parkinson’s disease

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作  者:王萌[1,2,3] 栗原博 李怡芳[1,2,3] 段文君[1,2,3] 何蓉蓉 WANG Meng;KURIHARA Hiroshi;LI Yi-fang;DUAN Wen-jun;HE Rong-rong(Guangdong Engineering Research Center of Chinese Medicine and Disease Susceptibility,Jinan University,Guangzhou 510632,China;Institute of Traditional Chinese Medicine and Natural Products,Jinan University,Guangzhou 510632,China;Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,Jinan University,Guangzhou 510632,China)

机构地区:[1]暨南大学,广东省疾病易感性及中医药研发工程技术研究中心,广东广州510632 [2]暨南大学,中药及天然药物研究所,广东广州510632 [3]暨南大学,广东省中药药效物质基础及创新药物研究重点实验室,广东广州510632

出  处:《药学学报》2022年第6期1557-1564,共8页Acta Pharmaceutica Sinica

基  金:国家自然科学基金资助项目(82125038,81873209,81903821);珠江创新团队项目(2017BT01Y036);珠江学者计划项目(GDUPS2019);广东省基础与应用基础研究基金项目(2021B1515120023,2019A1515010909);广州市科技计划-基础与应用基础研究资助项目(201903010062,907158833068)。

摘  要:磷脂重塑包括去酰化与再酰化两个过程,其通过改变磷脂特定位点的脂肪酸长度和种类而实现新生磷脂向成熟磷脂的转化,是磷脂代谢的关键步骤。磷脂不仅是生物膜的基本组成成分,还参与细胞内许多分子信号的转导,因此磷脂重塑障碍可影响细胞膜结构和功能以及膜蛋白活性等,引起一系列错综复杂的信号级联反应,并最终导致包括神经退行在内的许多病理学改变。本文综述了磷脂重塑的基本过程及参与磷脂重塑的钙非依赖磷脂酶A_(2)β(calcium independent group VIA phospholipase A_(2),iPLA_(2)β)、过氧化物酶6(peroxiredoxin 6,PRDX6)、钙非依赖磷脂酶A_(2)γ(calcium independent group VIB phospholipase A_(2),iPLA_(2)γ)和酰基辅酶A溶血心磷脂酰基转移酶1(lysocardiolipin acyltransferase1,ALCAT1)在帕金森病病理中的作用,其中编码iPLA_(2)β的基因PLA_(2)G6突变已被广泛报道与遗传性帕金森综合症14型(Parkinson disease-14)直接相关,本文重点讨论了iPLA_(2)β在帕金森病发生发展过程中的分子机制,主要涉及磷脂脂肪酸代谢紊乱、线粒体生理学异常及α-突触核蛋白(α-synuclein,α-Syn)聚集体形成路易小体(Lewy body,LB)等方面,有助于了解磷脂重塑在帕金森病中的作用,并为开发新型的帕金森病诊断和治疗策略提供新的线索。The remodeling of phospholipid includes two processes:deacylation and reacylation.It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids,which is a key step in phospholipid metabolism.Phospholipids are not only the basic components of biological membranes,but also participate in the transduction of many molecular signals in cells.Therefore,phospholipid remodeling disorders can affect the structure and function of cell membranes,as well as the activity of membrane proteins,causing a series of intricate signaling cascades,and finally lead to many pathological changes including neurodegeneration.This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes,calcium independent group VIA phospholipase A_(2)(iPLA_(2)β),peroxiredoxin 6(PRDX6),calcium independent group VIB phospholipase A_(2)(iPLA_(2)γ)as well as acyl-CoA lysocardiolipin acyltransferase 1(ALCAT1)in the pathology of Parkinson's disease.The mutations in the gene encoding iPLA_(2)β,PLA_(2)G6,have been widely reported to be directly related to hereditary Parkinson disease-14(PARK14).Here we focus on the molecular mechanism of iPLA_(2)β in the development of Parkinson's disease,mainly involving phospholipid fatty acid metabolism disorders,mitochondrial physiology abnormalities andα-synuclein aggregate formation and other aspects,which will help to understand the role of phospholipid remodeling in Parkinson's disease,and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

关 键 词:磷脂重塑 帕金森病 钙非依赖磷脂酶A_(2) 过氧化物酶6 Α-突触核蛋白 线粒体 

分 类 号:R966[医药卫生—药理学]

 

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