Self-Assembling Peptide Scaffold Carrying Neural-Cell Adhesion Molecule-Derived Mimetic-Peptide Transplantation Promotes Proliferation and Stimulates Neurite Extension by Modulating Tau Phosphorylation and Calpain/Glycogen Synthase Kinase 3 beta (GSK-3β) in Neurons

Xu, Jian; Feng, Jing; Liu, Yudong; Hu, Tao; Li, Mingjing; Li, Fan

doi:10.12659/aot.924093

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…Previous studies have reported that the synthetic NCAM-ligand or NCAM mimic may inhibit cell apoptosis in cerebellar and dopaminergic neurons by stimulating PI3K/Akt signaling pathway [ 59 , 60 ]. Recently, NCAM is also found to exert anti-apoptotic effects by modulating the activity of glycogen synthase kinase 3β (GSK3β) in dorsal root ganglion and spinal cord motor neurons, as well as in sympathetic neuron-like PC12 cells [ 61 , 62 ]. In light of these findings, studies investigating the contribution of PI3K/Akt, GSK3β, and other potential downstream signaling molecules to NCAM1-dependent neuroprotective effects in the hippocampus will be of considerable interest.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Xu¹,

Du²,

Liu³

et al. 2023

Cell Death Dis

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Neuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.

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Section: Discussionmentioning

confidence: 99%

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Xu¹,

Du²,

Liu³

et al. 2023

Cell Death Dis

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“…RADA16-I was modified with a neural cell adhesion molecule-derived (NCAM) mimetic peptide (SIDRVEPYSSTAQ) and loaded LiCl onto functionalized RADA16-I to form a drug-loaded hydrogel scaffold. The scaffold can reduce the phosphorylation of Tau by inhibiting the calpain/GSK-3β signaling pathway, thereby significantly promoting cell proliferation, inhibiting apoptosis, and significantly increasing axonal length, number, and branch number [ 68 ].…”

Section: Active Modification Of Rada16-i: Modification With Active Mo...mentioning

confidence: 99%

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example

Guo

et al. 2022

Polymers

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Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages, mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For the better and wider application of these promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-I as an example. For insufficient specific activity, RADA16-I can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or that can undergo chemical crosslinking were used to mix with RADA16-I to enhance the mechanical properties of RADA16-I. To improve the performance of RADA16-I as drug carriers, appropriate adjustment of the RADA16-I sequence and/or modification of the RADA16-I-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.

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“…RADA16-Ⅰ was modified with a neural cell adhesion molecule-derived (NCAM) mimetic peptide (SIDRVEPYSSTAQ) and loaded LiCl onto functionalized RADA16-I to form a drugloaded hydrogel scaffold. The scaffold can reduce the phosphorylation of Tau by inhibiting the calpain/GSK-3β signaling pathway, thereby significantly promoting cell proliferation, inhibiting apoptosis, and significantly increasing axonal length, number, and branch number [72].…”

Section: Resisting Negative Factorsmentioning

confidence: 99%

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-Ⅰ as an Example

Guo¹,

Ma²,

Hu³

et al. 2022

Preprint

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Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For better and wider application of this kind of promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-Ⅰ as an example. For the insufficient specific activity, RADA16-Ⅰ can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or materials that can undergo chemical crosslinking were used to mix with RADA16-Ⅰto enhance the mechanical properties of RADA16-Ⅰ. To improve the performance of RADA16-Ⅰ as drug carriers, appropriate adjustment of the RADA16-Ⅰ sequence and/ or modification of the RADA16-Ⅰ-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for the further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.

show abstract

Self-Assembling Peptide Scaffold Carrying Neural-Cell Adhesion Molecule-Derived Mimetic-Peptide Transplantation Promotes Proliferation and Stimulates Neurite Extension by Modulating Tau Phosphorylation and Calpain/Glycogen Synthase Kinase 3 beta (GSK-3β) in Neurons

Cited by 5 publications

References 39 publications

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Upregulation of KLK8 contributes to CUMS-induced hippocampal neuronal apoptosis by cleaving NCAM1

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-I as an Example

Modification Strategies for Ionic Complementary Self-Assembling Peptides: Taking RADA16-Ⅰ as an Example

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