Computational and mathematical modelling towards understanding the structure and dynamics of biological systems has significantly impacted on translational neuroscience to face novel approaches toward neurological disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD). In this study, a computational model of AD and PD have been modelled using biochemical systems theory, and shows how Tumour Necrosis Factor alpha (TNF훼) regulated neuroinflammation, oxidative stress and insulin pathways can dysregulate its downstream signalling cascade that lead to neurodegeneration observed in AD and PD. The experimental data for initial conditions for this model and validation of the model was based on data reported in literature. In simulations, elevations in the aggregations of major proteins involved in the pathology of AD and PD including amyloid beta, alpha synuclein, tau have been modelled. Abnormal aggregation of these proteins and hyperphosphorylation of tau were observed in the model. This aggregation may lead to developing Lewy bodies, fibrils, plaques and tangles inside neurons that trigger apoptosis. An increase in the concentrations of TNF훼 and glutamate during diseased conditions was noted in the model. Accumulation of these proteins may be related to the feedback mechanism of TNF훼 that initiates its own release and the production of excess glutamate. This could lead to the prolonged activation of microglia that result in death of surrounding neurons. With the elevation in reactive oxygen species, oxidative stress also increased. Simulations suggest insulin may be an important factor identifying neurodegeneration in AD and PD, through its action along with the neuroinflammation and oxidative stress. Low insulin level was noticed in the diseased condition due to abnormal protein aggregation that leads to TNFα release. Given the role towards better design of real experiments, accumulation of oligomers of mutated proteins in AD and PD activating microglia and secreting TNFα along with other cytokines map to oxidative stress that led to cell death.

用于理解生物系统的结构和动力学的计算和数学建模已极大地影响了转化神经科学，以面对应对诸如阿尔茨海默氏病（AD）和帕金森氏病（PD）等神经系统疾病的新方法。在这项研究中，已使用生化系统理论对AD和PD的计算模型进行了建模，并显示了肿瘤坏死因子α（TNF훼）调控神经炎症，氧化应激和胰岛素途径如何失调其下游信号传导级联反应，从而导致神经变性。 AD和PD。该模型的初始条件和模型验证的实验数据基于文献中报道的数据。在模拟中，AD和PD病理所涉及的主要蛋白质（包括淀粉样β）的聚集体升高，αsynuclein，tau已建模。在模型中观察到这些蛋白质的异常聚集和tau的过度磷酸化。这种聚集可导致神经元内部的路易体，原纤维，斑块和缠结的发展，从而触发细胞凋亡。在模型中注意到在患病期间TNF훼和谷氨酸盐的浓度增加。这些蛋白质的积累可能与TNF훼的反馈机制有关，后者启动自身的释放并产生过量的谷氨酸。这可能导致小胶质细胞活化时间延长，导致周围神经元死亡。随着活性氧种类的增加，氧化应激也增加。模拟结果表明，胰岛素可能是识别AD和PD神经变性的重要因素，通过其作用以及神经炎症和氧化应激。在疾病状态下，由于异常蛋白质聚集导致TNFα释放，胰岛素水平低。考虑到对更好地设计真实实验的作用，AD和PD激活的小胶质细胞和分泌TNFα以及其他细胞因子的突变蛋白的寡聚物的积累映射到氧化应激，导致细胞死亡。