Late phase cell cycle proteins in Proteotoxic control in Alzheimer’s Disease: a possible target for therapy?Name : Dr. Vladan Bajic
Affliation : Professor
University : University Of Belgrade
Country : Serbia
Alzheimer’s disease is represented by neuronal loss and this loss is correlated to a constant state of neuronal instability induced by intrinsic and extrinsic factors. Aneuploidy has been seen as a culprit of process leading to Alzheimer’s Disease (AD). It affects, primarily gene dosage of proteins (proteotoxicity) that are regulators of the APP metabolism but also may affect the protease and autophagy machinery in the AD cell. Late phase cell cycle proteins such as cohesin, centromere associated cycline-CDK11, Bub R1, Mad 2 and Mad 2B are proteins that regulate the anaphase promoting complex and the anaphase cell cycle checkpoint which therefore control proper chromosome segregation and separation. These Late phase cell cycle proteins are essential for maintaining genomic balance and are found when overexpressed lead to reduction in chromosome mis-segregation and hence aneuploidy. Also, knowledge that a number of these proteins that regulate cell division have secondary roles, i.e. coordinate a number of complex processes in neurogenesis (axonal pruning, dendric and spine morphogenesis and etc), neuronal survival and the maintenance of the post-mitotic state of neurons has led to question of how are these protein/s affected in Alzheimer’s Disease. Here we wish to present new and previous data on the possible roles of Late phase cell cycle proteins in normal and affected neurons in relation to the alteration of proteotoxic control that has been affected by aneuploidy. Therefore, understanding the mechanisms of proteotoxicity regulated by these proteins may represent a novel strategy for AD treatment.
My name is Vladan Bajic. I was born in Switzerland, 1961. Lived in Africa, USA and Europe, Serbia. I graduated in 1986 School of Veterinary Medicine and in 1992 became a Research Scientist for Animal Experimental Medicine in Galenika Pharmaceutical Company, Institute for Pharmaceutical Research, Biomedical Department, Belgrade, Serbia. In 1998 I have finished my Msc in Genetic Toxicology and my PhD in 2002, in CytopathoGenetics, on the genotoxic relevance of Centromere Instability *(CIN) in Normal Cells exposed to Cytostatics. This has lead to my present and future interest in Alzheimer’s Disease though the finding that CIN is present in AD patients. Still, I also worked on my managerial skills and became Director of Biomedical Research and Galenika Pharmaceuticals in 2003. In 2004 I became Assistant General Manager for R and D and a member of the Board of Directors, Galenika Pharmaceuticals. In 2007 I returned to Research and I was awarded a Fulbright Scholarship for Alzheimer’s Research. In 2011, I was awarded German Scholar Program DAAD for AD research. Both programs were related to CIN in AD. In 2012 I became Full Professor of Research. From 2013 to date at the Institute for Nuclear Research ‘’Vinca’’, Department of molecular genetics where Im working on the role of late phase cell cycle proteins in AD.