Shu Han

Corrigendum on: Zhou W, Qu H, Fu X-X, Xu M-M, Li Q, Jiang Y and Han S (2024), Neuroprotective effects of a novel peptide through the Rho-integrin-Tie2 and PI3K/Akt pathways in experimental autoimmune encephalomyelitis model. Front. Pharmacol. 15:1290128. doi: 10.3389/fphar.2024.1290128 In the published article, there was an error in Supplementary Figure S7 as published. The magnification of subfigure S of Supplementary Figure S7 is different from others. The corrected Supplementary Figure S7 and its caption Effects of C16, C16+Tie-2 inhibitor, and C16+PI3K inhibitor on neuron apoptosis induced by EAE. (A-J) TUNEL staining showed apoptotic neurons (double stained by hematoxylin-eosin staining). (K-T) Immunohistochemistry staining of cleaved caspase-3 detected apoptotic neurons in each group. (U-V) Quantification analysis of TUNEL and cleaved caspase-3-labeled cells in different groups. (Left, box plot; Right, dot plot). n = 5 per group. *, p < 0.05 vs. normal control group; #, p < 0.05 vs. vehicle group; &, p < 0.05 vs. C16 group; @, p < 0.05 vs. C16+Tie-2 inhibitor group. Tissues from the spinal cord and motor cortex were used for imaging analysis. Scale bar = 100 μm. Kruskal-Wallis nonparametric one-way ANOVA followed by post hoc analysis was used to analyze data presented as percentages. appear below.

Corrigendum on: Chen H, Fu X, Jiang J and Han S (2019) C16 Peptide Promotes Vascular Growth and Reduces Inflammation in a Neuromyelitis Optica Model. Front. Pharmacol. 10:1373. doi: 10.3389/fphar.2019.01373In the published article, there was an error in Supplementary Figure S1 as published. The magnification of subfigure B and G of Supplementary Figure S1 is different from others. The corrected Supplementary Figure S1 and its caption Immunofluorescence images of Tie2 expression in transverse sections through the anterior horn of the lumbar SC in (A - I) normal and NMO rats treated with (C, G) C16, (D, H) Tie2 KI + C16 and (E, I) LY294002 + C16 at 3 and 8 weeks P.I. Scale bar = 100 μm. (J) Plot of Tie2+ blood vessels. a, P < 0.05 versus normal group; b, P < 0.05 versus the vehicle-treated group; c, P < 0.05 versus the C16-treated group; d, P < 0.05 versus Tie2 KI + C16 group. Tie2 loss in the ON of vehicle-treated NMO rats is indicated by the arrow in B, F. appear below.

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvβ3 and α5β1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model.Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE.Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvβ3, and α5β1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16.Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

Gradual loss of neuronal structure and function due to impaired blood-brain barrier (BBB) and neuroinflammation are important factors in multiple sclerosis (MS) progression. Our previous studies demonstrated that the C16 peptide and angiopoietin 1 (Ang-1) compound (C + A) could modulate inflammation and vascular protection in many models of MS. In this study, nanotechnology and a novel nanovector of the leukocyte chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) were used to examine the effects of C + A on MS. The acute experimental autoimmune encephalomyelitis (EAE) model of MS was established in Lewis rats. The C + A compounds were conjugated to control nano-carriers and fMLP-nano-carriers and administered to animals by intravenous injection. The neuropathological changes in the brain cortex and spinal cord were examined using multiple approaches. The stimulation of vascular injection sites was examined using rabbits. The results showed that all C + A compounds (C + A alone, nano-carrier C + A, and fMLP-nano-carrier C + A) reduced neuronal inflammation, axonal demyelination, gliosis, neuronal apoptosis, vascular leakage, and BBB impairment induced by EAE. In addition, the C + A compounds had minimal side effects on liver and kidney functions. Furthermore, the fMLP-nano-carrier C + A compound had better effects compared to C + A alone and the nano-carrier C + A. This study indicated that the fMLP-nano-carrier C + A could attenuate inflammation-related pathological changes in EAE and may be a potential therapeutic strategy for the treatment of MS and EAE.

Background: Levodopa is regarded as a standard medication in Parkinson disease (PD) treatment. However, long-term administration of levodopa leads to levodopa-induced dyskinesia (LID), which can markedly affect patient quality of life. Previous studies have shown that neuroinflammation in the brain plays a role in LID and increases potential neuroinflammatory mediators associated with the side effects of levodopa. Objective: The treatment effect of C16 (a peptide that competitively binds integrin αvβ 3 and inhibits inflammatory cell infiltration) and angiopoietin-1 (Ang-1; a vascular endothelial growth factor vital for blood vessel protection), along with levodopa, was evaluated in a rodent model of PD. Methods: We administered a combination of C16 and Ang-1 in a rodent model of PD induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Seventy-five mice were randomly divided into five treatment groups: control, vehicle, levodopa, C16+Ang-1, and levodopa+C16+Ang-1. Behavioral, histological, and electrophysiological experiments were used to determine neuron function and recovery. Results: The results showed that C16+Ang-1 treatment alleviated neuroinflammation in the CNS and promoted the recovery effects of levodopa on neural function. Conclusion: Our study suggests that C16+Ang-1 can compensate for the shortcomings of levodopa, improve the CNS microenvironment, and ameliorate the effects of levodopa. This treatment strategy could be developed as a combinatorial therapeutic in the future.

Alzheimer’s disease (AD) is a neurological disorder characterized by neuronal cell death, tau pathology, and excessive inflammatory responses. Several vascular risk factors contribute to damage of the blood–brain barrier (BBB), secondary leak-out of blood vessels, and infiltration of inflammatory cells, which aggravate the functional disability and pathological changes in AD. Growth factor angiopoietin-1 (Ang-1) can stabilize the endothelium and reduce endothelial permeability by binding to receptor tyrosine kinase 2 (Tie2). C16 peptide (KAFDITYVRLKF) selectively binds to integrin ανβ3 and competitively inhibits leukocyte transmigration into the central nervous system by interfering with leukocyte ligands. In the present study, 45 male Sprague-Dawley (SD) rats were randomly divided into three groups: vehicle group, C16 peptide + Ang1 (C + A) group, and sham control group. The vehicle and C + A groups were subjected to two-vessel occlusion (2-VO) with artery ligation followed by Aβ1-42 injection into the hippocampus. The sham control group underwent sham surgery and injection with an equal amount of phosphate-buffered saline (PBS) instead of Aβ1-42. The C + A group was administered 1 mL of drug containing 2 mg of C16 and 400 µg of Ang-1 daily for 2 weeks. The sham control and vehicle groups were administered 1 mL of PBS for 2 weeks. Our results showed that treatment with Ang-1 plus C16 improved functional disability and reduced neuronal death by inhibiting inflammatory cell infiltration, protecting vascular endothelial cells, and maintaining BBB permeability. The results suggest that these compounds may be potential therapeutic agents for AD and warrant further investigation.