Cell Cycle Aberrations and the Impact of Oxidative Stress in Neurodegenerative Processes and Malignant Transformation of the Cell

Cell cycle aberrations in neurodegenerative diseases such as Alzheimer's disease (AD) include re-entry of neurons into the cell cycle, despite being highly differentiated cells in their quiescent. The mechanism of this mitotic disturbance is incompletely known, although a combination of two factors seems to have a crucial role: aberrant cell cycle regulation and oxidative stress. In neurons, these two factors, lead to dysfunction, decay, and ultimately cell death. Disorders of cell cycle regulation and oxidative stress also play a key role in the malignant alteration of cells. Under the proposed project, we aim to examine the following: (1) the mechanisms that lead to cell cycle aberrations of patients with neurodegenerative diseases; (2) the in vitro effects of particular hormones and antioxidants in healthy elderly and elderly AD patients (through a monitoring of cytogenetic changes); and (3) the degree of DNA damage in affected cells (using the Comet test). Furthermore, we shall examine the role of the stress proteins and proteins that regulate the cell cycle in malignant transformed cells. The results of the proposed research could contribute to a better understanding of changes in cells that are a consequence of oxidative stress and/or disorders of genetic control of cell cycle and would have significance in providing guidelines for the prevention, diagnosis, and treatment of neurodegenerative and malignant disorders.