Therapeutic potential of extracellular vesicles in neurological diseases

doi:10.12122/j.issn.1673-4254.2025.09.24

Abstract

Abstract:

Extracellular vesicles (EVs), nanoscale lipid bilayer vesicles actively secreted by organisms into the extracellular environment, are rich in specific bioactive substances, such as proteins, genetic materials and lipids. These vesicles are involved in intercellular interactions and can pass through the blood-brain barrier, and may thus potentially serve as important biological substances for treatment of neurological diseases. In this review, we summarize the biological origin of EVs and their therapeutic potential in neurological diseases, expound the possibility of EV-based treatment of neurological diseases using traditional Chinese medicine, and discuss the challenges and prospects of researches of EVs for the treating neurological diseases.

Key words: extracellular vesicles, neurological disorders, treatment, medicated therapy

Qingfeng DU, Chao YANG, Xueqing XIA, Ting WANG. Therapeutic potential of extracellular vesicles in neurological diseases[J]. Journal of Southern Medical University, 2025, 45(9): 2046-2054.

Figures/Tables 2

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Classification	Subgroup	Size (nm)	Biomarkers	Origin
Exomeres		-35	Hsp90-β	Endosomes
Exosomes	Exo-S	60-80	Tetraspanins, Tsg101, Alix, flotillin, Hsp70
Exosomes	Exo-L	90-120	Tetraspanins, Tsg101, Alix, Hsp70
Microvesicles		150-1000	Integrins, selectins, CD40	Plasma membrane
Apoptotic bodies		500-2000	Phosphatidylserine, genomic DNA	Plasma membrane, endoplasmic reticulum
Migrasomes		500-3000	Tetraspanins, chemokines, cytokines, growth factors, cholesterol	Retraction fibers

Classification	Subgroup	Size (nm)	Biomarkers	Origin
Exomeres		-35	Hsp90-β	Endosomes
Exosomes	Exo-S	60-80	Tetraspanins, Tsg101, Alix, flotillin, Hsp70
Exosomes	Exo-L	90-120	Tetraspanins, Tsg101, Alix, Hsp70
Microvesicles		150-1000	Integrins, selectins, CD40	Plasma membrane
Apoptotic bodies		500-2000	Phosphatidylserine, genomic DNA	Plasma membrane, endoplasmic reticulum
Migrasomes		500-3000	Tetraspanins, chemokines, cytokines, growth factors, cholesterol	Retraction fibers

Disease	Sources of EVs	Cargos	Mechanism and function	Referen-ces
Alzheimer's disease	Bone marrow MSCs		Reduced Aβ and amyloid deposition	48
	MSCs		MSC-derived exosomal miR-223 inhibited the apoptosis of neurons by targeting PTEN, activating the PI3K/Akt pathway	49
	Hippocampus neuron cell		Fe65-EXO-Cory-B blocked the natural interaction between Fe65 and APP, induceing autophagy in APP-expressing neuronal cells	50
	MSCs		Reduced plaque deposition and Aβ	51
	Macrophages	Silibinin	Reducing Aβ aggregation and deactivating astrocytes	52
	Cells	Curcumin	Inhibiting phosphorylation of the Tau protein through activating the AKT/GSK-3β pathway	53
	Rat plasma	Quercetin	Inhibiting cyclin-dependent kinase 5-mediated phosphorylation of Tau and reducing formation of insoluble neurofibrillary tangles	54
Parkinson's disease	Dendritic cells	shRNA minicircles	Decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons	56
	Epicatechin gallate		Inhibiting caspase 3, increase the Bcl-2/BAX ratioto reduce apoptosis	57
	MSCs		Stimulating ICAM1-SMAD3/ P38MAPK pathway	58
	Astrocytes		miR-200a-3p suppressed MKK4 expressions	59
	MSCs	Curcumin	PR-EXO/PP@Cur targets the reductionα-synuclein aggregates, promotes neuron function recovery, and alleviates the neuroinflammation	60
	MSCs	Dihydrotanshinone I	Inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra	61

Disease	Sources of EVs	Cargos	Mechanism and function	Referen-ces
Alzheimer's disease	Bone marrow MSCs		Reduced Aβ and amyloid deposition	48
	MSCs		MSC-derived exosomal miR-223 inhibited the apoptosis of neurons by targeting PTEN, activating the PI3K/Akt pathway	49
	Hippocampus neuron cell		Fe65-EXO-Cory-B blocked the natural interaction between Fe65 and APP, induceing autophagy in APP-expressing neuronal cells	50
	MSCs		Reduced plaque deposition and Aβ	51
	Macrophages	Silibinin	Reducing Aβ aggregation and deactivating astrocytes	52
	Cells	Curcumin	Inhibiting phosphorylation of the Tau protein through activating the AKT/GSK-3β pathway	53
	Rat plasma	Quercetin	Inhibiting cyclin-dependent kinase 5-mediated phosphorylation of Tau and reducing formation of insoluble neurofibrillary tangles	54
Parkinson's disease	Dendritic cells	shRNA minicircles	Decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons	56
	Epicatechin gallate		Inhibiting caspase 3, increase the Bcl-2/BAX ratioto reduce apoptosis	57
	MSCs		Stimulating ICAM1-SMAD3/ P38MAPK pathway	58
	Astrocytes		miR-200a-3p suppressed MKK4 expressions	59
	MSCs	Curcumin	PR-EXO/PP@Cur targets the reductionα-synuclein aggregates, promotes neuron function recovery, and alleviates the neuroinflammation	60
	MSCs	Dihydrotanshinone I	Inhibition of peripheral inflammatory cell infiltration, precise regulation of inflammatory microglia in the substantia nigra	61