Formal model of Parkinson's disease neurons unveils possible causality links in the pathophysiology of the disease
Nadal, M.; Kaminski Schierle, G. S.; Dikicioglu, D.
Show abstract
Parkinsons Disease is the second most common neurodegenerative disease after Alzheimers disease. Despite extensive research, the initial cause of the disease is still unknown, although substantial advances were made in understanding of its genetics and the cognate neurophysiological mechanisms. Determining the causality relationships and the chronological steps pertaining to Parkinsons Disease is essential for the discovery of novel drug targets. We developed a systematic in silico model based on available data, which puts the possible sequence of events occurring in a neuron during disease onset into light. This is the first ever attempt, to our knowledge, to model comprehensively the primary modifications in the molecular pathways that manifest in compromised neurons from the commencement of the disease to the consequences of its progression. We showed that our proposed disease pathway was relevant for unveiling yet incomplete knowledge on calcium homeostasis in mitochondria, ROS production and -synuclein misfolding. Graphical abstract HighlightsO_LIVarying calcium concentration in aging dopaminergic neurons triggers disease onset. C_LIO_LIROS production in the mitochondria potentially causes iron accumulation. C_LIO_LIIron homeostasis dysregulation is linked to -synuclein aggregation. C_LI
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Computational verification of large logical models - application to the prediction of T cell response to checkpoint inhibitors 93%
- An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow 92%
- Discrete dynamic model of the mammalian sperm acrosome reaction: the influence of acrosomal pH and biochemical heterogeneity 91%
Similar papers in this journal
- Virtual metabolic human dynamic model for pathological analysis and therapy design for diabetes 93%
- Mechanistic Modeling of Biochemical Systems Without A Priori Parameter Values Using the Design Space Toolbox v.3.0 93%
- Neural tube patterning: from a minimal model for rostrocaudal patterning towards an integrated 3D model 92%
Similar papers in this journal
- Dopamine depletion leads to pathological synchronization of distinct basal ganglia loops in the beta band 94%
- A novel yeast hybrid modeling framework integrating Boolean and enzyme-constrained networks enables exploration of the interplay between signaling and metabolism 93%
- Multi-scale model suggests the trade-off between protein and ATP demand as a driver of metabolic changes during yeast replicative ageing 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.