Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy

Biological modelling helps understanding complex processes, like energy metabolism, by predicting pathway compensations and equilibrium under given conditions. When deciphering metabolic adaptations, traditional experiments face challenges due to numerous enzymatic activities, needing modelling to a...

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Main Authors: Camille Siharath, Olivier Biondi, Sabine Peres
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Heliyon
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024169496
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author Camille Siharath
Olivier Biondi
Sabine Peres
author_facet Camille Siharath
Olivier Biondi
Sabine Peres
author_sort Camille Siharath
collection DOAJ
description Biological modelling helps understanding complex processes, like energy metabolism, by predicting pathway compensations and equilibrium under given conditions. When deciphering metabolic adaptations, traditional experiments face challenges due to numerous enzymatic activities, needing modelling to anticipate pathway behaviours and orientate research. This paper aims to implement a constraint-based modelling method of muscular energy metabolism, adaptable to individual situations, energy demands, and complex disease-specific metabolic alterations like muscular dystrophy calpainopathy. Our calpainopathy-like model not only confirms the ATP production defect under increasing energy demands, but suggests compensatory mechanisms through anaerobic glycolysis. However, excessive glycolysis indicates a need to enhance mitochondrial respiration, preventing excess lactate production common in several diseases. Our model suggests that moderate-intensity physiotherapy, known to improve aerobic performance and anaerobic buffering, combined with increased carbohydrate and amino acid sources, could be a potent therapeutic approach for calpainopathy.
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spelling doaj-art-f84c3d0757d74508aabb11b3a7a4f6582024-12-19T10:56:10ZengElsevierHeliyon2405-84402024-12-011024e40918Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathyCamille Siharath0Olivier Biondi1Sabine Peres2Laboratoire de Biométrie et de Biologie Évolutive, UMR CNRS 5558 Université Claude Bernard Lyon 1, 69622, Villeurbanne cedex, France; ERABLE, INRIA Lyon Centre, 69622, Villeurbanne cedex, FranceLaboratoire de Biologie de l'Exercice pour la Performance et la Santé (LBEPS), UMR, Université d'Evry, IRBA, Université de Paris Saclay, 91025, Evry-Courcouronnes, FranceLaboratoire de Biométrie et de Biologie Évolutive, UMR CNRS 5558 Université Claude Bernard Lyon 1, 69622, Villeurbanne cedex, France; ERABLE, INRIA Lyon Centre, 69622, Villeurbanne cedex, France; Corresponding author.Biological modelling helps understanding complex processes, like energy metabolism, by predicting pathway compensations and equilibrium under given conditions. When deciphering metabolic adaptations, traditional experiments face challenges due to numerous enzymatic activities, needing modelling to anticipate pathway behaviours and orientate research. This paper aims to implement a constraint-based modelling method of muscular energy metabolism, adaptable to individual situations, energy demands, and complex disease-specific metabolic alterations like muscular dystrophy calpainopathy. Our calpainopathy-like model not only confirms the ATP production defect under increasing energy demands, but suggests compensatory mechanisms through anaerobic glycolysis. However, excessive glycolysis indicates a need to enhance mitochondrial respiration, preventing excess lactate production common in several diseases. Our model suggests that moderate-intensity physiotherapy, known to improve aerobic performance and anaerobic buffering, combined with increased carbohydrate and amino acid sources, could be a potent therapeutic approach for calpainopathy.http://www.sciencedirect.com/science/article/pii/S2405844024169496
spellingShingle Camille Siharath
Olivier Biondi
Sabine Peres
Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
Heliyon
title Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
title_full Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
title_fullStr Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
title_full_unstemmed Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
title_short Modelling energy metabolism dysregulations in neuromuscular diseases: A case study of calpainopathy
title_sort modelling energy metabolism dysregulations in neuromuscular diseases a case study of calpainopathy
url http://www.sciencedirect.com/science/article/pii/S2405844024169496
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AT sabineperes modellingenergymetabolismdysregulationsinneuromusculardiseasesacasestudyofcalpainopathy