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100 kDa超滤物中的器官特异性小蛋白网络:功能分析及其对神经再生医学的意义

Organ-Specific Small Protein Networks in 100 kDa Ultrafiltrates: Functional Analysis and Implications for Neuroregenerative Medicine.

作者信息

Slivka Jakub Peter, Bauer Chris, Halhouli Tasneem, Younsi Alexander, Wong Michelle B F, Chan Mike K S, Skutella Thomas

机构信息

Reviva, Plzenska 47, 252 19 Chrastany, Czech Republic.

MicroDiscovery, 10405 Berlin, Germany.

出版信息

Int J Mol Sci. 2025 Jul 11;26(14):6659. doi: 10.3390/ijms26146659.

Abstract

In this research, the proteomic landscape of 100 kDa protein extract sourced from rabbit brain was compared to extracts from liver and from organ mixture (OM). Our aim was to compare the efficacy of Nanomised Organo Peptides (NOP) ultrafiltrates from two different tissues and a tissue mixture for inducing neurite outgrowth, and subsequently to identify the molecular networks and proteins that could explain such effects. Proteins were isolated by gentle homogenization followed by crossflow ultrafiltration. Proteomic evaluation involved gel electrophoresis, complemented by mass spectrometry and bioinformatics. GO (Gene Ontology) and protein analysis of the mass spectrometry results identified a diverse array of proteins involved in critical specific biological functions, including neuronal development, regulation of growth, immune response, and lipid and metal binding. Data from this study are accessible from the ProteomeXchange repository (identifier PXD051701). Our findings highlight the presence of small proteins that play key roles in metabolic processes and biosynthetic modulation. In vitro outgrowth experiments with neural stem cells (NSCs) showed that 100 kDa protein extracts from the brain resulted in a greater increase in neurite length compared to the liver and organ mixture extracts. The protein networks identified in the NOP ultrafiltrates may significantly improve biological therapeutic strategies related to neural differentiation and outgrowth. This comprehensive proteomic analysis of 100 kDa ultrafiltrates revealed a diverse array of proteins involved in key biological processes, such as neuronal development, metabolic regulation, and immune response. Brain-specific extracts demonstrated the capacity to promote neurite outgrowth in NSCs, suggesting potential application for neuroregenerative therapies. Our findings highlight the potential of small proteins and organ-specific proteins in the development of novel targeted treatments for various diseases, particularly those related to neurodegeneration and aging.

摘要

在本研究中,将源自兔脑的100 kDa蛋白质提取物的蛋白质组图谱与肝脏和器官混合物(OM)提取物进行了比较。我们的目的是比较来自两种不同组织和一种组织混合物的纳米化有机肽(NOP)超滤物诱导神经突生长的功效,随后鉴定能够解释此类效应的分子网络和蛋白质。通过温和匀浆,随后进行错流超滤来分离蛋白质。蛋白质组学评估包括凝胶电泳,并辅以质谱分析和生物信息学。基因本体论(GO)和质谱结果的蛋白质分析确定了一系列参与关键特定生物学功能的蛋白质,包括神经元发育、生长调节、免疫反应以及脂质和金属结合。本研究的数据可从蛋白质组交换库获取(标识符PXD051701)。我们的研究结果突出了在代谢过程和生物合成调节中起关键作用的小蛋白质的存在。用神经干细胞(NSC)进行的体外生长实验表明,与肝脏和器官混合物提取物相比,脑源性100 kDa蛋白质提取物导致神经突长度有更大增加。在NOP超滤物中鉴定出的蛋白质网络可能会显著改善与神经分化和生长相关的生物治疗策略。对100 kDa超滤物进行的这种全面蛋白质组学分析揭示了一系列参与关键生物学过程的蛋白质,如神经元发育、代谢调节和免疫反应。脑特异性提取物显示出促进NSC中神经突生长的能力,表明其在神经再生治疗中的潜在应用。我们的研究结果突出了小蛋白质和器官特异性蛋白质在开发针对各种疾病,特别是与神经退行性变和衰老相关疾病的新型靶向治疗中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aad1/12294768/da5d565a3953/ijms-26-06659-g001.jpg

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