Experimental in vivo models for understanding inter-molecular interactions and preventing multifactor disease development

Abstract

The increased spontaneous fragility in the centromere regions of the chromosomes predisposes to abnormal cellular division due to abnormal interaction with the mitotic spindle, which leads to number chromosomal aberrations. The abnormal structure of the microtubule-associated proteins (MAPs) could also be among the internal factors, predisposing to these pathologies. On the other hand, the increased frequency of the spontaneous chromosomal fragility suggests abnormal structure of the respective chromosomal/chromatin components and thus an increased risk about gene mutations and structural chromosomal aberrations. The spontaneous chromosomal fragility was tested by light microscopy observation of metaphases from peripheral blood lymphocytes of 8 patients with polygene pathologies (neoplasms, neuro-degenerative diseases, and neuro-psychiatric disorders) and of 18 healthy controls. In the tested patients was established significantly higher frequency of the spontaneous chromosomal fragility, including in the centromere chromosomal regions, compared to the controls. Different inter-molecular interactions, which could prevent the pathology appearance, were investigated by appropriate experimental in vivo models. As a whole, in the most cases, the presented data showed significantly lower average titers of anti-ganglioside antibodies and gangliosides in the samples from myocardium and liver than in the samples from brain and pancreas. By taking into consideration that the myocardium and liver are known as the most enriched of GSH anatomic organs, the presented data could be explained with the literature messages of higher amounts of de novo-synthesized free GSH tri-peptide in the same two organs. Moreover, a possibility about the production of antibodies/immunoglobulins by non-lymphoid types of cells, tissues, and organs in appropriate conditions was shown. Because the so-produced antibodies are out of the germinative centers in the specialized lymphoid tissues and organs, the control of their functions by small ions and molecules as gangliosides is very important. In the current study, the attention was particularly directed to the iteractions with the participation of gangliosides, the reduced form of the tri-peptide glutathione (GSH), and the protein HACE1. Besides the tumor-suppressor activity of protein HACE1, also its neuroprotective influence was proven, namely by interactions with specific molecules.