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一种用于整合突触小泡酸化和填充假定机制的细胞器酸化开放科学计算模型。

An Open-Science Computational Model of Organelle Acidification to Integrate Putative Mechanisms of Synaptic Vesicle Acidification and Filling.

作者信息

Baraglia Emanuele Carnevale, Fattorini Giorgia, Chattaraj Sandipan, Pasqualini Francesco, Conti Fiorenzo

机构信息

Synthetic Physiology Lab, Department of Civil Engineering and Architecture, University of Pavia, Pavia, Italy.

Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Ancona, Italy.

出版信息

Neurochem Res. 2025 Jun 5;50(3):181. doi: 10.1007/s11064-025-04432-9.

Abstract

Organelle acidification has essential implications for the development of degenerative disorders in the brain and heart, but the experimental characterization of these dynamic compartments in native-like contexts is challenging. Computational models can help organize and refine putative mechanisms of organelle acidifications in the same way they helped with brain and heart electrophysiology. Unfortunately, existing models of organelle acidification are not easy to access and operate. Here, we ported the existing model of lysosome acidification into an open-source Python implementation. Furthermore, we hosted this implementation in Google Colab, so everyone with a browser can simulate organelle acidification without a technical background. Finally, we demonstrate how this model can be extended to new organelle types by providing simulations of synaptic vesicle acidification and filling that incorporate different proposed modes of transport and can be fitted to recent experiments.

摘要

细胞器酸化对大脑和心脏退行性疾病的发展具有重要影响,但在类似天然环境中对这些动态区室进行实验表征具有挑战性。计算模型可以帮助整理和完善细胞器酸化的假定机制,就像它们在大脑和心脏电生理学中发挥的作用一样。不幸的是,现有的细胞器酸化模型不易获取和操作。在这里,我们将现有的溶酶体酸化模型移植到了开源的Python实现中。此外,我们将这个实现托管在谷歌Colab上,这样每个有浏览器的人都可以在没有技术背景的情况下模拟细胞器酸化。最后,我们通过提供突触小泡酸化和装填的模拟来展示如何将这个模型扩展到新的细胞器类型,这些模拟纳入了不同的运输模式,并可以与最近的实验相拟合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c203/12141144/889f8c881645/11064_2025_4432_Fig1_HTML.jpg

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