Academic Journal
Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer's Disease.
| العنوان: | Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer's Disease. |
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| المؤلفون: | FARINA, Sofia, VOORSLUIJS, Valerie, FIXEMER, Sonja, BOUVIER, David, Claus, Susanne, Ellisman, Mark H, BORDAS, Stéphane, SKUPIN, Alexander |
| المصدر: | PLoS Computational Biology, 19 (9), e1011464 (2023-09-20) |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2023 |
| المجموعة: | University of Luxembourg: ORBilu - Open Repository and Bibliography |
| مصطلحات موضوعية: | Humans, Astrocytes/metabolism, Brain/metabolism, Energy Metabolism, Alzheimer Disease/metabolism, Alzheimer, Disease progression, Homoeostasis, Mechanistics, Metabolic function, Molecular changes, Morphological changes, Morphology changes, Multiscale modeling, Alzheimer Disease, Astrocytes, Brain, Modeling and Simulation, Molecular Biology, Cellular and Molecular Neuroscience, Computational Theory and Mathematics, Life sciences, Biochemistry, biophysics & molecular biology, Sciences du vivant, Biochimie, biophysique & biologie moléculaire |
| الوصف: | peer reviewed ; Astrocytes with their specialised morphology are essential for brain homeostasis as metabolic mediators between blood vessels and neurons. In neurodegenerative diseases such as Alzheimer's disease (AD), astrocytes adopt reactive profiles with molecular and morphological changes that could lead to the impairment of their metabolic support and impact disease progression. However, the underlying mechanisms of how the metabolic function of human astrocytes is impaired by their morphological changes in AD are still elusive. To address this challenge, we developed and applied a metabolic multiscale modelling approach integrating the dynamics of metabolic energy pathways and physiological astrocyte morphologies acquired in human AD and age-matched control brain samples. The results demonstrate that the complex cell shape and intracellular organisation of energetic pathways determine the metabolic profile and support capacity of astrocytes in health and AD conditions. Thus, our mechanistic approach indicates the importance of spatial orchestration in metabolism and allows for the identification of protective mechanisms against disease-associated metabolic impairments. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1553-734X 1553-7358 |
| Relation: | https://dx.plos.org/10.1371/journal.pcbi.1011464; https://gitlab.lcsb.uni.lu/ICS-lcsb/energy-metabolism-model-astrocyte; urn:issn:1553-734X; urn:issn:1553-7358; https://orbilu.uni.lu/handle/10993/59130; info:hdl:10993/59130; https://orbilu.uni.lu/bitstream/10993/59130/1/Manuscript.pdf; info:pmid:37729344 |
| DOI: | 10.1371/journal.pcbi.1011464 |
| الاتاحة: | https://orbilu.uni.lu/handle/10993/59130 https://orbilu.uni.lu/bitstream/10993/59130/1/Manuscript.pdf https://doi.org/10.1371/journal.pcbi.1011464 |
| Rights: | open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CE449F5B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1553734X 15537358 |
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| DOI: | 10.1371/journal.pcbi.1011464 |