Modelling approach of the role of Ca2+ in cell signalling and in the onset of Alzheimer’s disease

par Dr Geneviève Dupont (Unité de Chronobiologie Théorique. Université Libre de Bruxelles)

jeudi 31 mars 2016, 14:00 → 15:00 Europe/Paris

Salle de séminaire 4ième étage (Bâtiment CEI-2 Antenne Inria Lyon)

Ca²⁺ is an ubiquitous intracellular messenger that mediates vital physiological functions in most cell types. Specificity is ensured by the high level of spatio-temporal organisation of the stimulus-triggered Ca²⁺ increases in the form of oscillations and waves. Modelling can be used to help understanding the molecular mechanisms responsible for these Ca²⁺ signals, as well as to back-up experimental investigations. In pathological situations, disruptions in Ca²⁺ homeostasis are often observed. In particular, it has been suggested that during the onset of Alzheimer’s disease, there is a positive feedback loop between intraneuronal Ca²⁺ and beta amyloids (Ab). By formalizing this loop in a minimal two variable model, we assessed the possible physiological consequences of this hypothesis and showed that it can account for a variety of in vivo observations related to this disease.

• De Caluwé J. and Dupont G. (2013) The progression towards Alzheimer's disease described as a bistable switch arising from the positive loop between amyloids and Ca²⁺. J. Theor. Biol. 331, 12-18.
• Dupont G. (2014) Modeling the intracellular organization of calcium signaling. WIREs Syst. Biol. Med., doi: 10.1002/wsbm.1261.
• Wacquier B., Combettes L., Tran Van Nhieu G. and Dupont G. (2016) Interplay between intracellular Ca²⁺ oscillations and Ca²⁺-stimulated mitochondrial metabolism. Scientific Reports 5, 19316.