外泌体在神经退行性疾病中的作用研究进展

doi:10.3724/SP.J.1123.2024.10035

摘要/Abstract

摘要：

外泌体是一种由细胞分泌的纳米级脂质双层囊泡,携带蛋白质、核酸、脂类等重要生物活性分子,广泛存在于血液、脑脊液等体液中。它们通过内吞作用、配体-受体相互作用或直接膜融合等多种机制,将生物活性分子传递给靶细胞,在细胞间通讯中发挥着至关重要的作用。作为天然的药物传递系统,外泌体具有生物相容性、高透过性、靶向性和含天然治疗分子等优势,能够提高药物递送的精确性和疗效,从而成为向中枢神经系统递送药物的理想载体。因此,外泌体在中枢神经系统疾病的诊断与治疗中显示出巨大的潜力。本文系统综述了近年来外泌体在神经退行性疾病中的研究进展,重点探讨了其在疾病发病机制、病程进展、诊断和治疗中的作用,旨在为神经退行性疾病的早期诊断与治疗提供理论依据与研究参考。

关键词: 外泌体, 神经退行性疾病, 生物标志物, 药物载体

Abstract:

Exosomes are nano-sized, lipid bilayer vesicles secreted by cells. They carry essential bioactive molecules, such as proteins, nucleic acids, and lipids, and are widely present in bodily fluids including blood and cerebrospinal fluid. Exosomes transfer bioactive molecules to target cells through various mechanisms, including endocytosis, ligand-receptor interactions, or direct membrane fusion, and play crucial roles in intercellular communication, including facilitating intercellular information exchange, maintaining nerve-cell function, participating in immune responses, and providing nutritional support. Exosomes significantly promote signal transmission and intercellular communication in the central nervous system and are involved in the pathogenesis and development of diseases by participating in the spread of pathological proteins, regulating neuroinflammation, and the deposition of pathological proteins. Therefore, exosomes play key roles in the occurrence and development of neurodegenerative diseases, and their contents, especially proteins and miRNAs, are specific for given pathological and physiological states and are relatively stable during extraction and analysis. Hence, exosomes are ideal tools for diagnosing diseases, staging their courses, and assisting prognosis. This article further explores exosomes derived from blood, saliva, urine, and cerebrospinal fluid as potential diagnostic biomarkers for neurodegenerative diseases. As natural drug-delivery systems, exosomes have the advantages of biocompatibility, ability to cross biological barriers, target specificity, stability, and containing natural therapeutic molecules, which can effectively improve the precision and efficacy of drug delivery and reduce side effects, making them an ideal carrier for delivering drugs to the central nervous system. Therefore, exosomes hold great potential in the diagnosis and treatment of central nervous system diseases. This article systematically reviews the latest advances in exosome research directed toward specific neurodegenerative diseases, focusing on their roles played in disease pathogenesis, progression, diagnosis, and treatment, with the aim of providing theoretical support and a reference for the early diagnosis and treatment of these diseases.

Key words: exosomes, neurodegenerative diseases, biomarkers, drug microcarrier

中图分类号:

O658

卜彩婷, 竺雪冬, 张倩颖, 邵文亚. 外泌体在神经退行性疾病中的作用研究进展[J]. 色谱, 2025, 43(5): 487-497.

BU Caiting, ZHU Xuedong, ZHANG Qianying, SHAO Wenya. Recent advances on the role of exosomes in neurodegenerative diseases[J]. Chinese Journal of Chromatography, 2025, 43(5): 487-497.

图/表 2

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Disease	Body fluid	Potential biomarkers	Sensitivity	Specificity	AUC	Ref.
AD	blood	Aβ42	-	-	0.930	[47]
		T-tau	-	-	0.890	[47]
		P-T181-tau	-	-	0.890	[47]
		P-IRS1, Caspase D, Syn	-	-	-	[50]
		BDNF, VEGF, TGF-β, GFAP, NfL	-	-	-	[51]
	CSF	miR-328-3p	-	-	0.702	[48]
		Aβ42, T-tau, P-tau	-	-	-	[49]
PD	saliva	α-syn oligomer	-	-	-	[53]
	blood	α-syn	0.67	0.71	0.675	[54]
		α-syn interacts with aggregated proteins	0.94	0.96	0.980	[55]
		PEDF, ApoD, C1q, IGLV1-33	-	-	-	[56]
		DJ-1	0.80	0.58	0.703	[57]
		(S)-(-)-2-hydroxyisocaproic acid	-	-	1	[60]
		miR-92a-3p, miR-24-3p	-	-	-	[61]
		miR-21-3p, miR-199a-5p, miR-425-5p, miR-483-5p,	0.89	0.90	0.910	[62]
		miR-22-3p, miR-29a-3p
	CSF	α-syn	-	-	-	[63]
		miR-409-3p	-	-	0.970	[64]
		miR-19b-3p	-	-	0.705	[64]
		miR-10a-5p	-	-	0.900	[64]
	urine	Ser(P)-1292 LRRK2	0.60	0.90	0.788	[58]
		PCSK1N, HNRNPA1, pPLA2G4A, pLTB4R, pPRR15	1	0.69	0.943	[59]
HD	CSF	miR-135b-3p, miR-140-5p	-	-	-	[65]
		CAG Repeat RNA, polyQ protein	-	-	-	[66]
ALS	blood	miR-27a-3p	-	-	-	[67]
	CSF	CUEDC2	-	-	-	[68]

Disease	Body fluid	Potential biomarkers	Sensitivity	Specificity	AUC	Ref.
AD	blood	Aβ42	-	-	0.930	[47]
		T-tau	-	-	0.890	[47]
		P-T181-tau	-	-	0.890	[47]
		P-IRS1, Caspase D, Syn	-	-	-	[50]
		BDNF, VEGF, TGF-β, GFAP, NfL	-	-	-	[51]
	CSF	miR-328-3p	-	-	0.702	[48]
		Aβ42, T-tau, P-tau	-	-	-	[49]
PD	saliva	α-syn oligomer	-	-	-	[53]
	blood	α-syn	0.67	0.71	0.675	[54]
		α-syn interacts with aggregated proteins	0.94	0.96	0.980	[55]
		PEDF, ApoD, C1q, IGLV1-33	-	-	-	[56]
		DJ-1	0.80	0.58	0.703	[57]
		(S)-(-)-2-hydroxyisocaproic acid	-	-	1	[60]
		miR-92a-3p, miR-24-3p	-	-	-	[61]
		miR-21-3p, miR-199a-5p, miR-425-5p, miR-483-5p,	0.89	0.90	0.910	[62]
		miR-22-3p, miR-29a-3p
	CSF	α-syn	-	-	-	[63]
		miR-409-3p	-	-	0.970	[64]
		miR-19b-3p	-	-	0.705	[64]
		miR-10a-5p	-	-	0.900	[64]
	urine	Ser(P)-1292 LRRK2	0.60	0.90	0.788	[58]
		PCSK1N, HNRNPA1, pPLA2G4A, pLTB4R, pPRR15	1	0.69	0.943	[59]
HD	CSF	miR-135b-3p, miR-140-5p	-	-	-	[65]
		CAG Repeat RNA, polyQ protein	-	-	-	[66]
ALS	blood	miR-27a-3p	-	-	-	[67]
	CSF	CUEDC2	-	-	-	[68]