Systems Biology of Parkinson's Disease by Wakoto Matsuda (auth.), Peter Wellstead, Mathieu Cloutier PDF

By Wakoto Matsuda (auth.), Peter Wellstead, Mathieu Cloutier (eds.)

ISBN-10: 1461434106

ISBN-13: 9781461434108

ISBN-10: 1461434114

ISBN-13: 9781461434115

The platforms Biology of Parkinson’s affliction could be underpinned by means of new size thoughts. this can be relatively precise of the pathology of Parkinson's sickness, the place fresh advancements in mind imaging have provided new insights into the morphology of dopaminergic neurons that experience profound implications for the unique vulnerability and position of this type of neurons.

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The key point from these three plots (second row in Fig. g. the two feedback loops in Fig. 4) is highly effective maintaining a constant level of ATP even under significant deterioration in brain energy metabolism. Simulations of combinations of risk factors (not shown) indicate that the steadystate regulatory system remains robust during combinations of risk, but is more strongly challenged and fails earlier as more risks are imposed. This in silico result suggests an additive effect when combinations of risk are applied.

Transient ATP Control During Signalling The two feedback loops in the brain energy metabolism prove themselves robustly capable to supply steady-state ATP requirements. Even with combinations of risk factors, the steady ATP levels maintain a good degree of resilience. However, when 2 Modelling and Simulation of Brain Energy Metabolism. . 33 Fig. 5 Steady “rest” state regulation and transient control of ATP in brain energy metabolism. Deterioration of energy regulation as PD risks factors grow with time: (a) loss of mitochondrial Complex I efficiency; (b) lower glucose (GLC) transport; and (c) loss of astrocytes connectivity from head trauma.

Now, we consider the “demand-side” argument. As far as it is known, neurons are the only 22 P. Wellstead and M. Cloutier cells to experience Parkinsonian damage. So to understand why energy should be a factor in PD, we consider why neurons are special from an energy demand perspective: Neurons work harder than other cells: Between 10 and 20 times harder in fact, with most of the additional energy requirement being needed to fuel neural signalling [18]. Their higher work rate implies that neurons would be more susceptible to failure if their energy metabolism were to be deficient.

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Systems Biology of Parkinson's Disease by Wakoto Matsuda (auth.), Peter Wellstead, Mathieu Cloutier (eds.)


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