Giulio Taglialatela, Ph.D.Assistant Professor Education• Ph.D., University of Rome, Italy, 1984 research interestsMy research interest focuses on apoptotic neuronal cell death in the aged central nervous system (CNS). Our laboratory at the University of Texas Medical Branch in Galveston, TX, is engaged in studies to determine the molecular and cellular mechanism(s) by which neurotrophins (particularly nerve growth factor, NGF) suppress apoptosis in neurons and to determine whether malfunctions of such neuro-protective mechanisms may be responsible for age-associated neurodegenerative events. Neurotrophins such as NGF, brain-derived neurotrophic factor (BDNF), and Neurotrophin-3 (NT-3) provide the necessary trophic support to certain classes of neurons throughout life. Most of the neurons that degenerate during aging depend on neurotrophins for their survival, thereby suggesting that impairments in neurotrophin mechanism of action during aging may result in neurodegeneration. Binding of neurotrophins to specific tyrosine kinase receptors (Trk) is required for some effects of neurotrophins to take place. In addition, all neurotrophins bind to a common low-affinity receptor (p75NGFR) whose function is unclear. Recent evidence suggests a link between p75NGFR and apoptotic events. Our aim is to determine whether neurotrophins can signal via p75NGFR receptors to prevent apoptosis. We use cultured cell models in which we suppress Trk or p75NGFR expression by antisense DNA technology and then determine responses to neurotrophins during an apoptotic challenge. We also study the effect of neurotrophins in apoptotic cells on second messenger systems (protein kinase C, phospholipase C, ceramide, etc.) and transcription factors (NF B, Fos, Jun, Octamer-1) that mediate neurotrophin responses. A model is shown in the following cartoon. In addition, we are also involved in studying the effects of neurotrophins on the stress activation of neuroendocrine axes as well as the impact of repeated stress exposures on neurotrophin activity in the CNS. These studies are aimed to determine how stress may result in neuronal impairments via a direct effect on neurotrophin homeostasis. Selected PublicationsTaglialatela G, Hibbert CJ, Werrbach-Perez K, Hutton LA, Perez-Polo JR(1995): Suppression of p140trkA does not abolish NGF rescue of serum-free PC12 cells and enable cells to respond to BDNF. J Neurochem, in press. Foreman PJ, Ramacci MT, Angelucci L, Perez-Polo JR, Taglialatela G (1995): ects of acetyl-l-carnitine treatment and stress exposure on the nerve growth factor receptor mRNA level in the central nervous system of aged rats. Prog. Neuro-Psychopharmacol. & Biol. Psychiat., 19(1):117-133. Taglialatela G, Perez-Polo JR (1994): Developmental profile of the hypothalamo-pituitary-adrenal axis response to nerve growth factor. Neurosci. Lett., 182:231-234. |