帕金森病相关外泌体研究进展

Research progress of exosomes in Parkinson disease

帕金森病(Parkinson disease,PD)是一种神经变性疾病,具有不可逆性、高发病率和高致残率的特点,早期识别和干预对改善PD意义重大。然而,目前临床上对PD的诊断缺乏客观的实验室检测指标,药物疗法对早期疾病修饰的证据尚不充分。外泌体是细胞产生、释放到胞外环境的囊泡,内含丰富的生物活性分子。中枢神经系统起源的外泌体,其中PD标志性蛋白质,如α-突触核蛋白、DJ-1和RNA分子水平的变化反映了机体病理生理状态的改变,是筛选疾病诊断、鉴别诊断、分期、预后等标志物的重要来源。间充质干细胞来源的外泌体具有与母细胞类似的组织修复、神经保护效应,而一些活性分子(如过氧化物酶、多巴胺、小干扰RNAs等)也可以外泌体为载体靶向运输到脑组织,针对PD不同的致病通路发挥作用。现综述外泌体在PD发生发展、诊断和治疗中的研究进展,探讨当前所面临的问题和未来可能的研究方向。

Parkinson disease(PD)is a neurodegenerative disease,characterized by irreversibility,high incidence and high morbidity.In this context,early identification and intervention are of great significance for ameliorating PD.However,at present,there is a lack of objective laboratory indexes in clinical practice,while the evidence for early disease modification by pharmacotherapy is insufficient.Exosomes are vesicles produced by cells and released to the extracellular,containing abundant bioactive molecules.Central nervous system derived exosomes are an important source for screening markers of disease diagnosis,differential diagnosis,staging and prognosis.Changes in their containing PD signature proteins,such as alpha-synuclein,DJ-1 and RNA molecules reflect the pathophysiological state of the organism.Exosomes from mesenchymal stem cells show the function of tissue repair and neuroprotection,paralleling to that of their parental cells.Meanwhile,therapeutic agents(such as catalase,dopamine,small interfering RNAs,etc).can be targeted to the brain by exosomes and act on different pathologic pathways of PD.This paper reviews the recent advances on exosomes in the occurrence,development,diagnosis and treatment of PD,and discusses the current problems and possible future research directions.