Mathematical Modelling Approach of WntSignalling PATHWAY Analyse in Alzheimer Disease

Abstract

Alzheimer disease is followed by accumulation of amyloid plaques and neurofibrillary tangles in neural cells of brain, what leads to toxicity and cell dead. These physical brain impairment or damage is followed with intellectual and cognition fall, and loss of capabilities. Beneath these impairments is production of amyloid beta protein and tau protein, that is interfered with signalling pathways that provide important functioning to organism, cells, or central nervous system, like cell proliferation, differentiation, adhesion, survival, and apoptosis, as an examples of functions that are provided with Wnt signaling pathway. Other pathways found to be included in pathology of Alzheimer’s disease are AMPK, mTOR, Sirtuin1, and PCB-1. They crosstalk with other molecular mechanisms, biological functions, and cell signaling in normal cell functioning and in disease. However, disease appears in case of abnormalities, irregularities or dysfunctions. Causes of Alzheimer disease are environmental, biological, or genetics factors. It can be also triggered earlier if other diseases are present like pneumonia, diabetes, injuries and strokes, HIV, or other specific diseases. It is interesting to examine connections between these abnormalities, irregularities, and dysfunctions with physical causes of disease, in case of Alzheimer disease formation of amyloid plaques and neurofibrillary tangles. Further, it is important to discover what causes dysfunctions of signaling pathways, or how they fight against risks and factors that cause the disease. In further research we will explore complexity and cross talk between the pathways and connection with diseases. In this paper we are particularly interested for Wnt signaling pathway since it has important cell functions, and cause transcription of genes that provide normal functioning and also have protective and neuroprotective effect in preventing and fighting off risk factors of disease. Wnt signaling is also found in other human diseases such as cancer, metabolic diseases, coronary disease, diabetes and obesity, etc. Our aim is to set framework for research examination of Alzheimer disease via understanding molecular mechanisms, biochemical reactions and mathematical modelling, and to perform dynamical analyze with simulation results, stability and bifurcation tests, in order to get better understanding of signaling pathways and connection with diseases.