Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Timeline showing the development and application of exosomes. AD: Alzheimer’s disease; EV: extracellular vesicle; MSCs-exo: mesenchymal stem cells derived exosomes; MVBs: multivesicular bodies; PD: Parkinson’s disease; TBI: traumatic brain injury.

Article Snippet: Consequently, stem cell-derived exosomes show significant potential for therapeutic applications in tissue regeneration (Vizoso et al., 2017).

Techniques: Derivative Assay

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Composition and biogenesis of exosomes. Following endocytosis, the endocytic material enters early endosomes, where the membrane buds inward to form internal vesicles, initiating endosomal maturation. MVBs are degraded through fusion with lysosomes or release exosomes by fusing with the plasma membrane. MVB: Multivesicular body.

Article Snippet: Consequently, stem cell-derived exosomes show significant potential for therapeutic applications in tissue regeneration (Vizoso et al., 2017).

Techniques: Membrane, Clinical Proteomics

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Overview of the role of exosomes in Alzheimer’s disease. (A) Pathophysiology: Exosomes released by brain cells cross the BBB and enter the peripheral circulatory system. (B) Treatment: Exosomes acting in conjunction with drugs or that are intravenously injected directly into mice can cross the BBB and target the damaged area to exert a therapeutic effect. BBB: Blood–brain barrier.

Article Snippet: Consequently, stem cell-derived exosomes show significant potential for therapeutic applications in tissue regeneration (Vizoso et al., 2017).

Techniques: Injection

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Schematic diagram of therapeutic strategies for exosomes in neurodegenerative diseases. Exosomes inhibit M1 microglial activation and increase dendritic spine density in Alzheimer’s disease models. The level of substantia nigra in the brain of Parkinson’s disease rats can be increased after exosome therapy. Exosomes can effectively reduce abnormal aggregation of huntington protein in Huntington’s disease mice. Exosomes significantly reduce demyelination in multiple sclerosis mouse models.

Article Snippet: Consequently, stem cell-derived exosomes show significant potential for therapeutic applications in tissue regeneration (Vizoso et al., 2017).

Techniques: Activation Assay

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The level of m 6 A modification is increased in activated microglia. (A) m 6 A RNA methylation quantitative experiments showed that the m 6 A modification level of LPS-treated (M1-like phenotype) BV2 cells was significantly increased compared with blank BV2 cells. (B) The expressions of AKBH5 and FTO mRNA in LPS-treated BV2 cells were significantly increased and decreased, respectively, compared with blank BV2 cells. (C) Western blot revealed significantly lower expression of FTO in LPS-treated BV2 cells with no changes in ALKBH5. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (unpaired Student’s t -test). (D) Motif central enrichment analysis revealed that the identified m 6 A peaks shared a common sequence element [U]GGAC[U]A. The consensus motif GGAC was detected. (E) The density distribution pattern of m 6 A peaks across the length of transcripts. Regions of the 5′-UTR, CDS, and 3′-UTR were binned into 30, 40, and 30 segments according to their relative lengths, respectively, and the percentage of m 6 A peaks fell within each region. (F) The m 6 A peak distribution in the 5′-UTR, start codon, coding sequences, stop codon, and 3′-UTR across the entire set of mRNA transcripts. (G) GO enrichment analysis of gene transcripts with more than a 2-fold expression change in LPS-stimulated BV2 cells compared with blank cells in the biological process category. (H) Heat map of differentially expressed genes in the blank and LPS-stimulated BV2 cells. AKBH5: alkB homolog 5 RNA demethylase; CDS: coding sequence; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; m 6 A: N 6 -methyladenosine; N.S.: not significant; UTR: untranslated regions.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Methylation, Western Blot, Expressing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates the microglial activation during the inflammatory response. (A, B) The efficiency of FTO knockdown (siFTO) and over-expression (oeFTO) in BV2 cells was measured by qRT-PCR (A) and western blotting (B). (C) Expression of M1 biomarkers in FTO overexpression and siFTO BV2 cells in response to LPS stimulation, as detected by flow cytometry. The siFTO group had a higher rate of M1 phenotype (CD11b + /CD86 + ) microglia in response to LPS stimulation compared with the negative control and the oeFTO groups. (D) The production of proinflammatory cytokines (IL-1β and TNF-α) increased remarkably in the siFTO group with LPS stimulation and decreased in the oeFTO group with LPS stimulation. (E) The production of anti-inflammatory cytokines (IL-10 and TGF-β1) decreased remarkably in the siFTO group with LPS stimulation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). (F) Immunofluorescence staining of CD86 (green) and Iba-1 (red) in the oeFTO, siFTO, and negative control groups with or without LPS treatment. The siFTO group had a higher rate of M1 phenotype (CD86 + /Iba-1 + ) microglia in response to LPS stimulation. Representative micrographs of CD86 + microglia (green) are shown. Scale bars: 50 µm. CD: Cluster of differentiation; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IL-1β: interleukin-1β; LPS: lipopolysaccharides; NC: normal control; N.S.: not significant; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Activation Assay, Knockdown, Over Expression, Quantitative RT-PCR, Western Blot, Expressing, Flow Cytometry, Negative Control, Immunofluorescence, Staining, Binding Assay, Control, Reverse Transcription, Polymerase Chain Reaction

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: ADAM17 is a downstream target of FTO-mediated m6A modification in microglia. (A) The m 6 A-modified genes were significantly different between control and LPS-treated BV2 cells. (B) The overlap between m6A-modified genes and inflammatory response–related genes was analyzed in control and LPS-treated BV2 cells using Venn diagrams. (C) Volcano plot of the gene enrichment pathway in control and LPS-treated BV2 cells. Compared with the control group, LPS-treated BV2 cells induced an up-regulation of the downstream effector molecules of the ADAM17/TNF-α/NF-κB pathway, including ADAM17, RELA and TNF-α. (D) m6A RNA-sequencing profile of the control and LPS-treated BV2 cells. By comparing m 6 A-sequencing with control BV2 cells, ADAM17, TNF-α and RELA mRNA in LPS-treated BV2 cells mainly concentrated in the coding sequences and 3′-UTR regions. (E, F) Compared with siFTO, siFTO + LPS BV2 cells, the levels of ADAM17, TNF-α, and RELA mRNA in oeFTO, oeFTO + LPS BV2 cells decreased (E) and protein levels also decreased (F). Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; mRNA: messenger ribonucleic acid; m 6 A: N 6 -methyladenosine; N.S.: not significant; NF-κB: nuclear factor kappa B; RELA: v-rel avian reticuloendotheliosis viral oncogene homolog A; TNF-α: tumor necrosis factor-α; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Control, RNA Sequencing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The epigenetic regulation of ADAM17 in an FTO-m 6 A-dependent mechanism. (A) Detection of ADAM17 precursor (pre-ADAM17) and mature transcripts (mat-ADAM17) by quantitative real-time polymerase chain reaction. The mat-ADAM17 mRNA was significantly enhanced in siFTO BV2 cells compared with oeFTO BV2 cells. (B) Detection of the half-life of ADAM17 in oeFTO and siFTO BV2 cells pretreated with actinomycin D and analyzed at 0, 2, 4, 6 and 8 hours. (C) The oeFTO and siFTO BV2 cells were pretreated with cycloheximide for 90 minutes; western blot analysis showed that ADAM17 protein had a longer half-life in the siFTO BV2 cells. (D) Schematic representation of positions of the m 6 A motifs within ADAM17 mRNA. (E) Schematic representation of the mutated (GGAC to GGTC) 3′-UTR pmirGLO vectors. (F) BV2 cells were transfected with pmirGLO-3′-UTR (wildtype, WT) or pmirGLO-3′-UTR-Mut1/2/3 (mutant, MUT1/2/3) reporter plasmids. The MUT3 construct had markedly decreased luciferase activity compared with WT BV2 cells. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; mRNA: messenger ribonucleic acid; N.S.: not significant; m6A: N6-methyladenosine; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Real-time Polymerase Chain Reaction, Western Blot, Transfection, Mutagenesis, Construct, Luciferase, Activity Assay

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: Inhibition of ADAM17 in vitro blocks microglial activation after FTO-m6A modification. (A, B) In situ hybridization results indicated that ADAM17 co-localized with FTO in oeFTO and siFTO BV2 cells treated with or without LPS. (A) Double staining of FISH and IF demonstrated that FTO overexpression combined with LPS stimulus increased the co-localization of FTO protein and ADAM17 mRNA. Scale bars: 20 µm. (B) Line profile of colocalization. (C, D) M1-like (CD86 + /Iba-1 + ) microglia in the siFTO + TAPI group decreased compared with the siFTO group (C). Scale bars: 50 µm. The protein levels of CD86, ADAM17, and iNOS were down-regulated, while the expression of CD206 and Arg-1 increased in the siFTO + TAPI group (D). (E) ELISA results showed that the siFTO + TAPI group had significantly reduced expression of IL-1β, TNF-α, and IL-6 and increased expression of TGF-β1 compared with the siFTO group. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FISH: fluorescence in situ hybridization; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IF: immunofluorescence; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1β; LPS: lipopolysaccharides; N.S.: not significant; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Inhibition, In Vitro, Activation Assay, Modification, In Situ Hybridization, Double Staining, Over Expression, Expressing, Enzyme-linked Immunosorbent Assay, Fluorescence, Binding Assay, Immunofluorescence

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates neuroinflammation in vivo by targeting ADAM17 in microglia after TBI. (A) Western blotting demonstrated that NADP intervention inhibited ADAM17, TNF-α, and NF-κB p65. (B) Schematic illustration of the isolation of exosomes in the supernatant of NC and oeADAM17 BV2 cells; exosomes were isolated and characterized through TEM, NTA, and exosomal biomarkers assay. Scale bars: 200 nm. (C) Compared with the TBI + NADP group, the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of ADAM17, CD86, and iNOS and decreased the expression of CD206 and Arg-1. (D) ELISA results showed that the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of TNF-α, IL-1β, IL-6 and IFN-γ. (E) The apoptosis rate of neurons in the TBI + NADP + exo-oeADAM17 group was significantly higher than that in the TBI + NADP group on day 3 after TBI. Representative photomicrographs of the Nissl-stained neurons are shown. The arrows indicate apoptotic neurons. Scale bar: 50 µm. (F) Representative photos of Evans blue dye extravasation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; Arg-1: arginase-1; Bcl-2: B-cell lymphoma-2; Bax: BCL2-Associated X; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IFN-γ: interferon-γ; IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; NADP: nicotinamide adenine dinucleotide phosphate; NC: negative control; NF-κB: nuclear factor kappa-B; NTA: nanoparticle tracking analysis; N.S.: not significant; TEM: transmission electron microscope; TBI: traumatic brain injury; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: In Vivo, Western Blot, Isolation, Expressing, Enzyme-linked Immunosorbent Assay, Staining, Binding Assay, Negative Control, Transmission Assay, Microscopy

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The level of m 6 A modification is increased in activated microglia. (A) m 6 A RNA methylation quantitative experiments showed that the m 6 A modification level of LPS-treated (M1-like phenotype) BV2 cells was significantly increased compared with blank BV2 cells. (B) The expressions of AKBH5 and FTO mRNA in LPS-treated BV2 cells were significantly increased and decreased, respectively, compared with blank BV2 cells. (C) Western blot revealed significantly lower expression of FTO in LPS-treated BV2 cells with no changes in ALKBH5. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (unpaired Student’s t -test). (D) Motif central enrichment analysis revealed that the identified m 6 A peaks shared a common sequence element [U]GGAC[U]A. The consensus motif GGAC was detected. (E) The density distribution pattern of m 6 A peaks across the length of transcripts. Regions of the 5′-UTR, CDS, and 3′-UTR were binned into 30, 40, and 30 segments according to their relative lengths, respectively, and the percentage of m 6 A peaks fell within each region. (F) The m 6 A peak distribution in the 5′-UTR, start codon, coding sequences, stop codon, and 3′-UTR across the entire set of mRNA transcripts. (G) GO enrichment analysis of gene transcripts with more than a 2-fold expression change in LPS-stimulated BV2 cells compared with blank cells in the biological process category. (H) Heat map of differentially expressed genes in the blank and LPS-stimulated BV2 cells. AKBH5: alkB homolog 5 RNA demethylase; CDS: coding sequence; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; m 6 A: N 6 -methyladenosine; N.S.: not significant; UTR: untranslated regions.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Methylation, Western Blot, Expressing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates the microglial activation during the inflammatory response. (A, B) The efficiency of FTO knockdown (siFTO) and over-expression (oeFTO) in BV2 cells was measured by qRT-PCR (A) and western blotting (B). (C) Expression of M1 biomarkers in FTO overexpression and siFTO BV2 cells in response to LPS stimulation, as detected by flow cytometry. The siFTO group had a higher rate of M1 phenotype (CD11b + /CD86 + ) microglia in response to LPS stimulation compared with the negative control and the oeFTO groups. (D) The production of proinflammatory cytokines (IL-1β and TNF-α) increased remarkably in the siFTO group with LPS stimulation and decreased in the oeFTO group with LPS stimulation. (E) The production of anti-inflammatory cytokines (IL-10 and TGF-β1) decreased remarkably in the siFTO group with LPS stimulation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). (F) Immunofluorescence staining of CD86 (green) and Iba-1 (red) in the oeFTO, siFTO, and negative control groups with or without LPS treatment. The siFTO group had a higher rate of M1 phenotype (CD86 + /Iba-1 + ) microglia in response to LPS stimulation. Representative micrographs of CD86 + microglia (green) are shown. Scale bars: 50 µm. CD: Cluster of differentiation; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IL-1β: interleukin-1β; LPS: lipopolysaccharides; NC: normal control; N.S.: not significant; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Activation Assay, Knockdown, Over Expression, Quantitative RT-PCR, Western Blot, Expressing, Flow Cytometry, Negative Control, Immunofluorescence, Staining, Binding Assay, Control, Reverse Transcription, Polymerase Chain Reaction

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: ADAM17 is a downstream target of FTO-mediated m6A modification in microglia. (A) The m 6 A-modified genes were significantly different between control and LPS-treated BV2 cells. (B) The overlap between m6A-modified genes and inflammatory response–related genes was analyzed in control and LPS-treated BV2 cells using Venn diagrams. (C) Volcano plot of the gene enrichment pathway in control and LPS-treated BV2 cells. Compared with the control group, LPS-treated BV2 cells induced an up-regulation of the downstream effector molecules of the ADAM17/TNF-α/NF-κB pathway, including ADAM17, RELA and TNF-α. (D) m6A RNA-sequencing profile of the control and LPS-treated BV2 cells. By comparing m 6 A-sequencing with control BV2 cells, ADAM17, TNF-α and RELA mRNA in LPS-treated BV2 cells mainly concentrated in the coding sequences and 3′-UTR regions. (E, F) Compared with siFTO, siFTO + LPS BV2 cells, the levels of ADAM17, TNF-α, and RELA mRNA in oeFTO, oeFTO + LPS BV2 cells decreased (E) and protein levels also decreased (F). Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; mRNA: messenger ribonucleic acid; m 6 A: N 6 -methyladenosine; N.S.: not significant; NF-κB: nuclear factor kappa B; RELA: v-rel avian reticuloendotheliosis viral oncogene homolog A; TNF-α: tumor necrosis factor-α; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Control, RNA Sequencing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The epigenetic regulation of ADAM17 in an FTO-m 6 A-dependent mechanism. (A) Detection of ADAM17 precursor (pre-ADAM17) and mature transcripts (mat-ADAM17) by quantitative real-time polymerase chain reaction. The mat-ADAM17 mRNA was significantly enhanced in siFTO BV2 cells compared with oeFTO BV2 cells. (B) Detection of the half-life of ADAM17 in oeFTO and siFTO BV2 cells pretreated with actinomycin D and analyzed at 0, 2, 4, 6 and 8 hours. (C) The oeFTO and siFTO BV2 cells were pretreated with cycloheximide for 90 minutes; western blot analysis showed that ADAM17 protein had a longer half-life in the siFTO BV2 cells. (D) Schematic representation of positions of the m 6 A motifs within ADAM17 mRNA. (E) Schematic representation of the mutated (GGAC to GGTC) 3′-UTR pmirGLO vectors. (F) BV2 cells were transfected with pmirGLO-3′-UTR (wildtype, WT) or pmirGLO-3′-UTR-Mut1/2/3 (mutant, MUT1/2/3) reporter plasmids. The MUT3 construct had markedly decreased luciferase activity compared with WT BV2 cells. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; mRNA: messenger ribonucleic acid; N.S.: not significant; m6A: N6-methyladenosine; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Real-time Polymerase Chain Reaction, Western Blot, Transfection, Mutagenesis, Construct, Luciferase, Activity Assay

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: Inhibition of ADAM17 in vitro blocks microglial activation after FTO-m6A modification. (A, B) In situ hybridization results indicated that ADAM17 co-localized with FTO in oeFTO and siFTO BV2 cells treated with or without LPS. (A) Double staining of FISH and IF demonstrated that FTO overexpression combined with LPS stimulus increased the co-localization of FTO protein and ADAM17 mRNA. Scale bars: 20 µm. (B) Line profile of colocalization. (C, D) M1-like (CD86 + /Iba-1 + ) microglia in the siFTO + TAPI group decreased compared with the siFTO group (C). Scale bars: 50 µm. The protein levels of CD86, ADAM17, and iNOS were down-regulated, while the expression of CD206 and Arg-1 increased in the siFTO + TAPI group (D). (E) ELISA results showed that the siFTO + TAPI group had significantly reduced expression of IL-1β, TNF-α, and IL-6 and increased expression of TGF-β1 compared with the siFTO group. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FISH: fluorescence in situ hybridization; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IF: immunofluorescence; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1β; LPS: lipopolysaccharides; N.S.: not significant; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Inhibition, In Vitro, Activation Assay, Modification, In Situ Hybridization, Double Staining, Over Expression, Expressing, Enzyme-linked Immunosorbent Assay, Fluorescence, Binding Assay, Immunofluorescence

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates neuroinflammation in vivo by targeting ADAM17 in microglia after TBI. (A) Western blotting demonstrated that NADP intervention inhibited ADAM17, TNF-α, and NF-κB p65. (B) Schematic illustration of the isolation of exosomes in the supernatant of NC and oeADAM17 BV2 cells; exosomes were isolated and characterized through TEM, NTA, and exosomal biomarkers assay. Scale bars: 200 nm. (C) Compared with the TBI + NADP group, the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of ADAM17, CD86, and iNOS and decreased the expression of CD206 and Arg-1. (D) ELISA results showed that the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of TNF-α, IL-1β, IL-6 and IFN-γ. (E) The apoptosis rate of neurons in the TBI + NADP + exo-oeADAM17 group was significantly higher than that in the TBI + NADP group on day 3 after TBI. Representative photomicrographs of the Nissl-stained neurons are shown. The arrows indicate apoptotic neurons. Scale bar: 50 µm. (F) Representative photos of Evans blue dye extravasation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; Arg-1: arginase-1; Bcl-2: B-cell lymphoma-2; Bax: BCL2-Associated X; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IFN-γ: interferon-γ; IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; NADP: nicotinamide adenine dinucleotide phosphate; NC: negative control; NF-κB: nuclear factor kappa-B; NTA: nanoparticle tracking analysis; N.S.: not significant; TEM: transmission electron microscope; TBI: traumatic brain injury; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: In Vivo, Western Blot, Isolation, Expressing, Enzyme-linked Immunosorbent Assay, Staining, Binding Assay, Negative Control, Transmission Assay, Microscopy

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The level of m 6 A modification is increased in activated microglia. (A) m 6 A RNA methylation quantitative experiments showed that the m 6 A modification level of LPS-treated (M1-like phenotype) BV2 cells was significantly increased compared with blank BV2 cells. (B) The expressions of AKBH5 and FTO mRNA in LPS-treated BV2 cells were significantly increased and decreased, respectively, compared with blank BV2 cells. (C) Western blot revealed significantly lower expression of FTO in LPS-treated BV2 cells with no changes in ALKBH5. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (unpaired Student’s t -test). (D) Motif central enrichment analysis revealed that the identified m 6 A peaks shared a common sequence element [U]GGAC[U]A. The consensus motif GGAC was detected. (E) The density distribution pattern of m 6 A peaks across the length of transcripts. Regions of the 5′-UTR, CDS, and 3′-UTR were binned into 30, 40, and 30 segments according to their relative lengths, respectively, and the percentage of m 6 A peaks fell within each region. (F) The m 6 A peak distribution in the 5′-UTR, start codon, coding sequences, stop codon, and 3′-UTR across the entire set of mRNA transcripts. (G) GO enrichment analysis of gene transcripts with more than a 2-fold expression change in LPS-stimulated BV2 cells compared with blank cells in the biological process category. (H) Heat map of differentially expressed genes in the blank and LPS-stimulated BV2 cells. AKBH5: alkB homolog 5 RNA demethylase; CDS: coding sequence; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; m 6 A: N 6 -methyladenosine; N.S.: not significant; UTR: untranslated regions.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Methylation, Western Blot, Expressing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates the microglial activation during the inflammatory response. (A, B) The efficiency of FTO knockdown (siFTO) and over-expression (oeFTO) in BV2 cells was measured by qRT-PCR (A) and western blotting (B). (C) Expression of M1 biomarkers in FTO overexpression and siFTO BV2 cells in response to LPS stimulation, as detected by flow cytometry. The siFTO group had a higher rate of M1 phenotype (CD11b + /CD86 + ) microglia in response to LPS stimulation compared with the negative control and the oeFTO groups. (D) The production of proinflammatory cytokines (IL-1β and TNF-α) increased remarkably in the siFTO group with LPS stimulation and decreased in the oeFTO group with LPS stimulation. (E) The production of anti-inflammatory cytokines (IL-10 and TGF-β1) decreased remarkably in the siFTO group with LPS stimulation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). (F) Immunofluorescence staining of CD86 (green) and Iba-1 (red) in the oeFTO, siFTO, and negative control groups with or without LPS treatment. The siFTO group had a higher rate of M1 phenotype (CD86 + /Iba-1 + ) microglia in response to LPS stimulation. Representative micrographs of CD86 + microglia (green) are shown. Scale bars: 50 µm. CD: Cluster of differentiation; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IL-1β: interleukin-1β; LPS: lipopolysaccharides; NC: normal control; N.S.: not significant; qRT-PCR: quantitative reverse transcription-polymerase chain reaction; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Activation Assay, Knockdown, Over Expression, Quantitative RT-PCR, Western Blot, Expressing, Flow Cytometry, Negative Control, Immunofluorescence, Staining, Binding Assay, Control, Reverse Transcription, Polymerase Chain Reaction

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: ADAM17 is a downstream target of FTO-mediated m6A modification in microglia. (A) The m 6 A-modified genes were significantly different between control and LPS-treated BV2 cells. (B) The overlap between m6A-modified genes and inflammatory response–related genes was analyzed in control and LPS-treated BV2 cells using Venn diagrams. (C) Volcano plot of the gene enrichment pathway in control and LPS-treated BV2 cells. Compared with the control group, LPS-treated BV2 cells induced an up-regulation of the downstream effector molecules of the ADAM17/TNF-α/NF-κB pathway, including ADAM17, RELA and TNF-α. (D) m6A RNA-sequencing profile of the control and LPS-treated BV2 cells. By comparing m 6 A-sequencing with control BV2 cells, ADAM17, TNF-α and RELA mRNA in LPS-treated BV2 cells mainly concentrated in the coding sequences and 3′-UTR regions. (E, F) Compared with siFTO, siFTO + LPS BV2 cells, the levels of ADAM17, TNF-α, and RELA mRNA in oeFTO, oeFTO + LPS BV2 cells decreased (E) and protein levels also decreased (F). Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; LPS: lipopolysaccharides; mRNA: messenger ribonucleic acid; m 6 A: N 6 -methyladenosine; N.S.: not significant; NF-κB: nuclear factor kappa B; RELA: v-rel avian reticuloendotheliosis viral oncogene homolog A; TNF-α: tumor necrosis factor-α; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Modification, Control, RNA Sequencing, Sequencing

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: The epigenetic regulation of ADAM17 in an FTO-m 6 A-dependent mechanism. (A) Detection of ADAM17 precursor (pre-ADAM17) and mature transcripts (mat-ADAM17) by quantitative real-time polymerase chain reaction. The mat-ADAM17 mRNA was significantly enhanced in siFTO BV2 cells compared with oeFTO BV2 cells. (B) Detection of the half-life of ADAM17 in oeFTO and siFTO BV2 cells pretreated with actinomycin D and analyzed at 0, 2, 4, 6 and 8 hours. (C) The oeFTO and siFTO BV2 cells were pretreated with cycloheximide for 90 minutes; western blot analysis showed that ADAM17 protein had a longer half-life in the siFTO BV2 cells. (D) Schematic representation of positions of the m 6 A motifs within ADAM17 mRNA. (E) Schematic representation of the mutated (GGAC to GGTC) 3′-UTR pmirGLO vectors. (F) BV2 cells were transfected with pmirGLO-3′-UTR (wildtype, WT) or pmirGLO-3′-UTR-Mut1/2/3 (mutant, MUT1/2/3) reporter plasmids. The MUT3 construct had markedly decreased luciferase activity compared with WT BV2 cells. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; FTO: the fat mass and obesity-related protein; mRNA: messenger ribonucleic acid; N.S.: not significant; m6A: N6-methyladenosine; UTR: untranslated region.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Real-time Polymerase Chain Reaction, Western Blot, Transfection, Mutagenesis, Construct, Luciferase, Activity Assay

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: Inhibition of ADAM17 in vitro blocks microglial activation after FTO-m6A modification. (A, B) In situ hybridization results indicated that ADAM17 co-localized with FTO in oeFTO and siFTO BV2 cells treated with or without LPS. (A) Double staining of FISH and IF demonstrated that FTO overexpression combined with LPS stimulus increased the co-localization of FTO protein and ADAM17 mRNA. Scale bars: 20 µm. (B) Line profile of colocalization. (C, D) M1-like (CD86 + /Iba-1 + ) microglia in the siFTO + TAPI group decreased compared with the siFTO group (C). Scale bars: 50 µm. The protein levels of CD86, ADAM17, and iNOS were down-regulated, while the expression of CD206 and Arg-1 increased in the siFTO + TAPI group (D). (E) ELISA results showed that the siFTO + TAPI group had significantly reduced expression of IL-1β, TNF-α, and IL-6 and increased expression of TGF-β1 compared with the siFTO group. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. * P < 0.05, ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student–Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FISH: fluorescence in situ hybridization; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IF: immunofluorescence; iNOS: inducible nitric oxide synthase; IL-1β: interleukin-1β; LPS: lipopolysaccharides; N.S.: not significant; TGF-β1: transforming growth factor-β1; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: Inhibition, In Vitro, Activation Assay, Modification, In Situ Hybridization, Double Staining, Over Expression, Expressing, Enzyme-linked Immunosorbent Assay, Fluorescence, Binding Assay, Immunofluorescence

Journal: Neural Regeneration Research

Article Title: Fat mass and obesity–mediated N 6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

doi: 10.4103/NRR.NRR-D-23-01854

Figure Lengend Snippet: FTO regulates neuroinflammation in vivo by targeting ADAM17 in microglia after TBI. (A) Western blotting demonstrated that NADP intervention inhibited ADAM17, TNF-α, and NF-κB p65. (B) Schematic illustration of the isolation of exosomes in the supernatant of NC and oeADAM17 BV2 cells; exosomes were isolated and characterized through TEM, NTA, and exosomal biomarkers assay. Scale bars: 200 nm. (C) Compared with the TBI + NADP group, the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of ADAM17, CD86, and iNOS and decreased the expression of CD206 and Arg-1. (D) ELISA results showed that the TBI + NADP + exo-oeADAM17 group showed significantly increased expression of TNF-α, IL-1β, IL-6 and IFN-γ. (E) The apoptosis rate of neurons in the TBI + NADP + exo-oeADAM17 group was significantly higher than that in the TBI + NADP group on day 3 after TBI. Representative photomicrographs of the Nissl-stained neurons are shown. The arrows indicate apoptotic neurons. Scale bar: 50 µm. (F) Representative photos of Evans blue dye extravasation. Values are expressed as mean ± SD from at least three independent experiments and the dots represent the value of each experiment. ** P < 0.01, *** P < 0.001 (one-way analysis of variance followed by Student Newman–Keuls tests). ADAM17: A disintegrin and metalloproteases 17; Arg-1: arginase-1; Bcl-2: B-cell lymphoma-2; Bax: BCL2-Associated X; CD: cluster of differentiation; ELISA: enzyme-linked immunosorbent assay; FTO: the fat mass and obesity-related protein; Iba-1: ionized calcium-binding adapter molecule 1; IFN-γ: interferon-γ; IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; NADP: nicotinamide adenine dinucleotide phosphate; NC: negative control; NF-κB: nuclear factor kappa-B; NTA: nanoparticle tracking analysis; N.S.: not significant; TEM: transmission electron microscope; TBI: traumatic brain injury; TNF-α: tumor necrosis factor-α.

Article Snippet: ADAM17-overexpressing BV2 cell–derived exosomes extracted by Exoquick exosome precipitation solution (System Biosciences, Palo Alto, CA, USA) were applied at 20 μg per 20 g body weight (intracerebroventricular injection) for in vivo treatment 30 minutes after surgery, and the vector transfected group was used as negative control.

Techniques: In Vivo, Western Blot, Isolation, Expressing, Enzyme-linked Immunosorbent Assay, Staining, Binding Assay, Negative Control, Transmission Assay, Microscopy

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Timeline showing the development and application of exosomes. AD: Alzheimer’s disease; EV: extracellular vesicle; MSCs-exo: mesenchymal stem cells derived exosomes; MVBs: multivesicular bodies; PD: Parkinson’s disease; TBI: traumatic brain injury.

Article Snippet: Research demonstrated increased concentrations of purinergic receptor P2X7 in oligodendrocyte-derived exosomes from MS patients compared with healthy individuals (Agliardi et al., 2024); thus, the levels of exosome-associated purinergic receptor P2X7 may serve as a biomarker for this disease.

Techniques: Derivative Assay

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Composition and biogenesis of exosomes. Following endocytosis, the endocytic material enters early endosomes, where the membrane buds inward to form internal vesicles, initiating endosomal maturation. MVBs are degraded through fusion with lysosomes or release exosomes by fusing with the plasma membrane. MVB: Multivesicular body.

Article Snippet: Research demonstrated increased concentrations of purinergic receptor P2X7 in oligodendrocyte-derived exosomes from MS patients compared with healthy individuals (Agliardi et al., 2024); thus, the levels of exosome-associated purinergic receptor P2X7 may serve as a biomarker for this disease.

Techniques: Membrane, Clinical Proteomics

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Overview of the role of exosomes in Alzheimer’s disease. (A) Pathophysiology: Exosomes released by brain cells cross the BBB and enter the peripheral circulatory system. (B) Treatment: Exosomes acting in conjunction with drugs or that are intravenously injected directly into mice can cross the BBB and target the damaged area to exert a therapeutic effect. BBB: Blood–brain barrier.

Article Snippet: Research demonstrated increased concentrations of purinergic receptor P2X7 in oligodendrocyte-derived exosomes from MS patients compared with healthy individuals (Agliardi et al., 2024); thus, the levels of exosome-associated purinergic receptor P2X7 may serve as a biomarker for this disease.

Techniques: Injection

Journal: Neural Regeneration Research

Article Title: Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods

doi: 10.4103/NRR.NRR-D-24-00720

Figure Lengend Snippet: Schematic diagram of therapeutic strategies for exosomes in neurodegenerative diseases. Exosomes inhibit M1 microglial activation and increase dendritic spine density in Alzheimer’s disease models. The level of substantia nigra in the brain of Parkinson’s disease rats can be increased after exosome therapy. Exosomes can effectively reduce abnormal aggregation of huntington protein in Huntington’s disease mice. Exosomes significantly reduce demyelination in multiple sclerosis mouse models.

Article Snippet: Research demonstrated increased concentrations of purinergic receptor P2X7 in oligodendrocyte-derived exosomes from MS patients compared with healthy individuals (Agliardi et al., 2024); thus, the levels of exosome-associated purinergic receptor P2X7 may serve as a biomarker for this disease.

Techniques: Activation Assay