Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions

Munder, Anna; Moskovitz, Yoni; Meir, Aviv; Kahremany, Shirin; Levy, Laura M.; Kolitz‐Domb, Michal; Cohen, Guy; Shtriker, Efrat; Viskind, Olga; Lellouche, Jean‐Paul; Senderowitz, Hanoch; Chessler, Steven; Korshin, É. E.; Ruthstein, Sharon; Gruzman, Arie

doi:10.1039/c8md00419f

Cited by 5 publications

(4 citation statements)

References 112 publications

(117 reference statements)

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“…Furthermore, studying the mechanisms underlying the low- to high-grade PanIN transition might provide innovative therapeutic opportunities to delay or reverse PanIN progression, which could include strategies based on restoring NLGN2-mediated signaling. This idea is supported by the results of studies focusing on the role of NLGN2 in insulin secretion and on the potential of NLGN2 mimetics as tools for treating patients with diabetes (Munder et al, 2017 ; Munder et al, 2019 ).…”

Section: Discussionmentioning

confidence: 82%

A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia

Middonti,

Astanina,

Vallariello

et al. 2024

EMBO Rep

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Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a dismal prognosis that arises from precursor lesions called pancreatic intraepithelial neoplasias (PanINs). Progression from low- to high-grade PanINs is considered as tumor initiation, and a deeper understanding of this switch is needed. Here, we show that synaptic molecule neuroligin-2 (NLGN2) is expressed by pancreatic exocrine cells and plays a crucial role in the regulation of contact inhibition and epithelial polarity, which characterize the switch from low- to high-grade PanIN. NLGN2 localizes to tight junctions in acinar cells, is diffusely distributed in the cytosol in low-grade PanINs and is lost in high-grade PanINs and in a high percentage of advanced PDACs. Mechanistically, NLGN2 is necessary for the formation of the PALS1/PATJ complex, which in turn induces contact inhibition by reducing YAP function. Our results provide novel insights into NLGN2 functions outside the nervous system and can be used to model PanIN progression.

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Section: Discussionmentioning

confidence: 82%

A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia

Middonti,

Astanina,

Vallariello

et al. 2024

EMBO Rep

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“…As was mentioned in the study on the treatment of eye-related conditions for corneal fibroblasts, the modification of PAMAM with the suitable peptide is beneficial for their proliferation. A modified oligopeptide (HAS-28) derived from neuroligin-2 ( Figure 35 d) attached to G5 PAMAM proved very advantageous for pancreatic β-cell culture, functional maturation, as well as glucose-stimulated insulin secretion [ 292 ]. Another peptide sequence, fibroblast inhibitor (isoleucine-lysine-valine-alanine-valine (IKVAV)) was attached peripherally to a polylysine dendrimer.…”

Section: Hepatic Aortic Neural and Pancreatic Tissue Engineeringmentioning

confidence: 99%

Dendritic Polymers in Tissue Engineering: Contributions of PAMAM, PPI PEG and PEI to Injury Restoration and Bioactive Scaffold Evolution

et al. 2023

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The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Perhaps the most important implementations are those that involve interactions with the regenerative mechanisms of cells. In general, they are non-toxic or exhibit very low toxicity. Thus, they allow unhindered and, in many cases, faster cell proliferation, a property that renders them ideal materials for tissue engineering scaffolds. Their resemblance to proteins permits the synthesis of derivatives that mimic collagen and elastin or are capable of biomimetic hydroxy apatite production. Due to their distinctive architecture (core, internal branches, terminal groups), dendritic polymers may play many roles. The internal cavities may host cell differentiation genes and antimicrobial protection drugs. Suitable terminal groups may modify the surface chemistry of cells and modulate the external membrane charge promoting cell adhesion and tissue assembly. They may also induce polymer cross-linking for healing implementation in the eyes, skin, and internal organ wounds. The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will also be exposed to the incorporation of methods for establishment of biomaterials, functionalization strategies, and the synthetic paths for organizing assemblies from biocompatible building blocks and natural metabolites.

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“…As was previously mentioned for other types of cells such as corneal fibroblasts, for instance, the modification of PAMAM with the suitable peptide is beneficial for their proliferation. A modified oligopeptide (HAS-28) derived from neuroligin-2 (Figure 35d) attached to G5 PAMAM proved very advantageous for pancreatic β-cell culture, functional maturation as well as glucose-stimulated insulin secretion [270]. Another peptide sequence, fibroblast inhibitor (isoleucine-lysine-valine-alanine-valine (IKVAV)) was attached peripherally to a polylysine dendrimer.…”

Section: Hepatic Aortic Neural and Pancreatic Tissue Engineeringmentioning

confidence: 99%

Dendritic Polymers Applications in Tissue Engineering

Arkas¹,

Vardavoulias²,

Kythreoti³

et al. 2022

Preprint

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The capability of radially polymerized bio-dendrimers and hyperbranched polymers for medical applications is well established. Among them, perhaps the most important are those that involve interactions with the regenerative mechanisms of cells. Dendritic polymers due to their distinctive architecture may play a multitude of roles such as protein biomimicry (collagen, elastin, hydroxy apatite production), gene and drug delivery (cell differentiation, antimicrobial protection), surface chemistry and charge modulation (adhesion to cells and tissues), polymer cross-linking (eye, skin and internal organ wound healing). The review highlights all the different categories of hard and soft tissues that may be remediated with their contribution. The reader will be also exposed to the incorporation methods to established biomaterials such as scaffolds, the functionalization strategies, and the synthetic paths for the assembly from biocompatible building blocks and natural metabolites.

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Neuroligin-2-derived peptide-covered polyamidoamine-based (PAMAM) dendrimers enhance pancreatic β-cells' proliferation and functions

Abstract: The nanoscale composite improved β-cell functions in terms of rate of proliferation, glucose-stimulated insulin secretion, resistance to cellular stress and functional maturation.

Cited by 5 publications

References 112 publications

A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia

A neuroligin-2-YAP axis regulates progression of pancreatic intraepithelial neoplasia

Dendritic Polymers in Tissue Engineering: Contributions of PAMAM, PPI PEG and PEI to Injury Restoration and Bioactive Scaffold Evolution

Dendritic Polymers Applications in Tissue Engineering

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