Exosomal microRNAs in common mental disorders: Mechanisms, biomarker potential and therapeutic implications

Table 1 Summary of changes of exosomal microRNAs in Alzheimer's disease-related animal experiments

	miRNAs	Alteration	Model	Type tissue	Significance	Ref.
Intercellular communication	miR-135a	Increase	AD mouse models, human patients	CSF, serum, plasma	ATP-binding cassette transporter-A1 reduces the false negatives of exosomal miRNAs. Possible biomarker for AD	Liu et al[33]
	miR-193b	Increase	Cell models, AD mouse models, human patients	CSF, serum, cell	Possible biomarker for AD	Liu et al[55]
	miR-770-3p		AD mouse models	Brain tissue	As the downstream target of circ-Epc1, overexpression of circ-Epc1 affects M1 microglia and forms AD	Liu et al[56]
	miR-29	Decrease	AD rice models	Hippocampus	Exosomal miR-29 has protective effects on amyloid pathogenesis	Jahangard et al[57]
	miR-185-5p	Decrease	AD mouse models, AD cell models, human patients	Brain tissue, cell, serum and CSF	The expression of exosomal miR-185-5p was decreased by binding of APP 3’UTRs to miR-185-5p	Ding et al[58]
	miR-532-5p		AD mouse models	Brain tissue	The exosomal miR-532-5p targets EPHA4, and reduces EPHA4 its expression. Possible biomarker of AD	Liang et al[59]
	miR1385p		AD mouse models, cell models	Brain tissue, hippocampus, cell	By targeting Tau as a protective factor for AD. Possible therapeutic targets	Meng et al[60]
	miR-451a, miR-19a-3p		AD mouse models	Hippocampus	Possible biomarker for AD	Yan et al[61]
	miR-29b-2		Cell models	Cell	Reduces PSEN1 levels and inhibits secretory enzymes. Possible therapeutic targets	Lin et al[62]
	miR-196b-5p, miR-339-3p, miR-34a-5p, miR-376b-3p, miR-677-5p, miR-721		AD mouse models	Urine	Urinary exosomal miRNAs are promising to supplement or replace invasive cerebrospinal fluid. Possible biomarker for AD	Song et al[63]
Inflammatory response	miR-146a	Increase	AD mouse models	Hippocampus	Macrophage tolerance to TLR4 was induced	Yang et al[46]
	miR-124-3p		AD mouse models	Brain tissue	Neurodegeneration is mitigated by targeting Rela/ApoE signaling pathways to transfer into hippocampal neurons	Ge et al[64]
	miR-124	Increase	AD cell models	Cell	Regulation by the secretome miR-124-3p released through the AD cell models. A promising therapy in AD	Garcia et al[65]
	miR-21	Increase	AD mouse models	Brain tissue, hippocampus	Take part in immune processes. Possible biomarker for AD	Garcia et al[66]
	miR-146a-5p		AD mouse models, AD cell models	Cell, brain tissue, hippocampus, plasma	Targeted regulation of the HIF1α/mtROS pathway and improvement of NLRP3 inflammasome and inflammatory factors can alleviate cognitive impairment in IH mice	Zhang et al[67]
	miR-223		Cell models	Cell	Yb-1-mediated microglial exosomal sorting of miR-223 improves nerve cell damage repair and is a promising therapeutic target for AD	Wei et al[68]
	miR-223	Decrease	AD cell models	Cell	It acts as a protective factor for AD through the PI3K/Akt signaling pathway	Wei et al[47]
	miR-146a	Increase	AD mouse models	Hippocampus, CSF	Exosomal transfer of miR-146a is involved in the correction of cognitive dysfunction in AD	Nakano et al[69]
	miR-22		AD mouse models	CSF and peripheral blood	MiR-22-loaded ADMSC-derived exosomes can reduce the release of inflammatory cytokines by inhibiting pyroptosis	Zhai et al[48]
	miR-7670-3p		AD mouse models	Brain tissue	MiR-7700-3p reduces ATF6 expression, protects the integrity of dendritic spines in cortical and hippocampal neurons, and ultimately improves cognitive function	Chen et al[52]
Others	miR-124	Increase	AD cell models	Cell	A novel diagnostic biomarker in circulating exosomes is a potential therapeutic target for AD whenever its deregulation is determined	Garcia et al[70]
	miR-1306-5p	Decrease	Cell models, human patients	Cell, serum	CircAXL promotes the inhibition of PDE4A by targeting miR-1306-5p. Possible biomarker for AD	Meng et al[71]
	miR-211-5p		AD cell models	Cell	Inhibition of miR-211-5p may improve the efficacy of HUCMSC-derived exosomes in the treatment of AD by increasing the expression of NEP	Chen et al[72]

miRNA: MicroRNA; AD: Alzheimer’s disease; CSF: Cerebrospinal fluid; ATP: Adenosine triphosphate; APP: Amyloid precursor protein; 3’UTR: 3’untranslated region; NLRP3: NOD-like receptor thermal protein domain associated protein 3; TLR4: Toll-like receptor 4; HIF1α: Hypoxia inducible factor-1α; mtROS: Mitochondrial reactive oxygen species; PI3K: Phosphatidylinositol 3-kinase; Akt: Protein kinase B; ADMSC: Adipose derived mesenchymal stem cells; HUCMSC: Human umbilical cord mesenchymal stem cells; NEP: Neprilysin.