PROTECTIVE EFFECT OF THE BRN-3A TRANSCRIPTION FACTOR IN NEURONAL CELLS

Diseasese such as Alzheimer's and Parkinson's diseases involve the death of nerve cells in the brain (central nervous system). The host laboratory has previously shown that the Brn-3a transcription factor can protect nerve cells of the peripheral nervous system (PNS) from death induced by different stimuli. Interestingly the overexpression of Brn-3a in cultured cells is able per-se to protect cells from apoptotic stimuli such as serum whithdrawal. I will test wether Brn-3a can also protect from death cells of the central nervous system (CNS). I will prepare an herpes simplex virus (defective of two lytic protein) expressing Brn-3a both in the sense and anti-sense orientation under the control of a cytomegalovirus immediate-early promoter. The viruses expressing either sense or antisense Brn-3a will be used to infect cells derived from the CNS. The infected cells will undergo a number of treatments in order to check if the overexpression of Brn-3a is able to protect cells of the CNS. The antisense viruses will instead allow us to understand the physiological role of Brn-3a. In the case of encouraging results I will check the effect of the overexpression of Brn-3a in the CNS of living animals. This work will allow the deeper comprehension of the role of Brn-3a in the central nervous system and if even in this case is able to protect cells from apoptotic stimuli.