TY - JOUR
T1 - Calcium-mediated mitochondrial energy deficiency in Parkinson's and Alzheimer's diseases
T2 - Insights from computational modelling
AU - Voorsluijs, Valérie
AU - Skupin, Alexander
N1 - Funding
AS and VV acknowledge the support from the Luxembourg National Research Fund (FNR) through the ReFoRMCaS project (C23/BM/18093639/ReForMCaS).
Publisher Copyright:
© 2025 The Authors
PY - 2025/1/10
Y1 - 2025/1/10
N2 - Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders worldwide and are characterised by progressive cognitive and functional impairments caused by neuronal loss. Energy deficiency is a predominant hallmark of their pathophysiology and plays a central role in the development of the disease, notably by mitochondrial dysfunction enhancing protein aggregation and oxidative stress which trigger subsequently immune responses and neuronal loss. Quantifying this energetic deficiency and identifying specific causative mechanisms from the complex network of interacting metabolic and regulatory pathways at play is rather challenging, where integrative mathematical modelling represents a powerful tool to support these investigations. Here, we review the latest developments in integrative modelling in brain bioenergetics in relation to Alzheimer's and Parkinson's diseases where we focus on the regulatory role of Ca2+ signalling. Finally, we discuss recent challenges and future directions to improve the current understanding of the energy-deficiency theory of neurodegeneration.
AB - Alzheimer's and Parkinson's diseases are the most prevalent neurodegenerative disorders worldwide and are characterised by progressive cognitive and functional impairments caused by neuronal loss. Energy deficiency is a predominant hallmark of their pathophysiology and plays a central role in the development of the disease, notably by mitochondrial dysfunction enhancing protein aggregation and oxidative stress which trigger subsequently immune responses and neuronal loss. Quantifying this energetic deficiency and identifying specific causative mechanisms from the complex network of interacting metabolic and regulatory pathways at play is rather challenging, where integrative mathematical modelling represents a powerful tool to support these investigations. Here, we review the latest developments in integrative modelling in brain bioenergetics in relation to Alzheimer's and Parkinson's diseases where we focus on the regulatory role of Ca2+ signalling. Finally, we discuss recent challenges and future directions to improve the current understanding of the energy-deficiency theory of neurodegeneration.
KW - Computational modelling
KW - Energy deficiency
KW - Metabolic reprogramming
KW - Mitochondria
KW - Neurodegeneration, Calcium
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=85214585838&partnerID=8YFLogxK
U2 - 10.1016/j.coisb.2024.100539
DO - 10.1016/j.coisb.2024.100539
M3 - Review article
AN - SCOPUS:85214585838
SN - 2452-3100
VL - 40
JO - Current Opinion in Systems Biology
JF - Current Opinion in Systems Biology
M1 - 100539
ER -