Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.

Neurodegenerative diseases are a group of disorders characterized by progressive degeneration or death of neurons. The complexity of clinical symptoms and irreversibility of disease progression significantly affects individual lives, leading to premature mortality. The prevalence of neurodegenerativ...

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Main Authors: Peng Ren, Xuehua Cui, Xia Liang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1012743
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author Peng Ren
Xuehua Cui
Xia Liang
author_facet Peng Ren
Xuehua Cui
Xia Liang
author_sort Peng Ren
collection DOAJ
description Neurodegenerative diseases are a group of disorders characterized by progressive degeneration or death of neurons. The complexity of clinical symptoms and irreversibility of disease progression significantly affects individual lives, leading to premature mortality. The prevalence of neurodegenerative diseases keeps increasing, yet the specific pathogenic mechanisms remain incompletely understood and effective treatment strategies are lacking. In recent years, convergent experimental evidence supports the "prion-like transmission" assumption that abnormal proteins induce misfolding of normal proteins, and these misfolded proteins propagate throughout the neural networks to cause neuronal death. To elucidate this dynamic process in vivo from a computational perspective, researchers have proposed three connectome-based biophysical models to simulate the spread of pathological proteins: the Network Diffusion Model, the Epidemic Spreading Model, and the agent-based Susceptible-Infectious-Removed model. These models have demonstrated promising predictive capabilities. This review focuses on the explanations of their fundamental principles and applications. Then, we compare the strengths and weaknesses of the models. Building upon this foundation, we introduce new directions for model optimization and propose a unified framework for the evaluation of connectome-based biophysical models. We expect that this review could lower the entry barrier for researchers in this field, accelerate model optimization, and thereby advance the clinical translation of connectome-based biophysical models.
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spelling doaj-art-1b980ed11aad416e8c629dbcd7aa9fc52025-08-20T03:52:37ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-01-01211e101274310.1371/journal.pcbi.1012743Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.Peng RenXuehua CuiXia LiangNeurodegenerative diseases are a group of disorders characterized by progressive degeneration or death of neurons. The complexity of clinical symptoms and irreversibility of disease progression significantly affects individual lives, leading to premature mortality. The prevalence of neurodegenerative diseases keeps increasing, yet the specific pathogenic mechanisms remain incompletely understood and effective treatment strategies are lacking. In recent years, convergent experimental evidence supports the "prion-like transmission" assumption that abnormal proteins induce misfolding of normal proteins, and these misfolded proteins propagate throughout the neural networks to cause neuronal death. To elucidate this dynamic process in vivo from a computational perspective, researchers have proposed three connectome-based biophysical models to simulate the spread of pathological proteins: the Network Diffusion Model, the Epidemic Spreading Model, and the agent-based Susceptible-Infectious-Removed model. These models have demonstrated promising predictive capabilities. This review focuses on the explanations of their fundamental principles and applications. Then, we compare the strengths and weaknesses of the models. Building upon this foundation, we introduce new directions for model optimization and propose a unified framework for the evaluation of connectome-based biophysical models. We expect that this review could lower the entry barrier for researchers in this field, accelerate model optimization, and thereby advance the clinical translation of connectome-based biophysical models.https://doi.org/10.1371/journal.pcbi.1012743
spellingShingle Peng Ren
Xuehua Cui
Xia Liang
Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
PLoS Computational Biology
title Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
title_full Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
title_fullStr Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
title_full_unstemmed Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
title_short Connectome-based biophysical models of pathological protein spreading in neurodegenerative diseases.
title_sort connectome based biophysical models of pathological protein spreading in neurodegenerative diseases
url https://doi.org/10.1371/journal.pcbi.1012743
work_keys_str_mv AT pengren connectomebasedbiophysicalmodelsofpathologicalproteinspreadinginneurodegenerativediseases
AT xuehuacui connectomebasedbiophysicalmodelsofpathologicalproteinspreadinginneurodegenerativediseases
AT xialiang connectomebasedbiophysicalmodelsofpathologicalproteinspreadinginneurodegenerativediseases