Giulio Taglialatela, Ph.D.
Giulio Taglialatela, Ph.D.
•Doctorate in Biological Sciences (Pharmacology),
University of Rome “La Sapienza”, Italy, 1986
•Post-Doctoral Training, University of Rome “La Sapienza”, 1986-1988
•Post-Doctoral Training, University of Texas Medical Branch, 1988-1990
About the Lab
Our main research focus is to study molecular events underlying neuronal dysfunction/death and the pathological progression of neurodegenerative diseases, with particular attention to Alzheimer Disease (AD), Parkinson Disease (PD) and Prion Disease. Collectively, these diseases are characterized by the abnormal presence, misfolding and aggregation into insoluble deposits of amyloid proteins; well characterized examples are amyloid beta (Ab) and senile plaques in AD and a-synuclein and Lewis bodies in PD. While macroscopic amyloid aggregates are a neuropathological signature of these diseases, recent evidence suggests that small oligomeric assemblies, precursors to the large amyloid fibrils forming the plaques, may be the main offending species. Notably, oligomers of the AD’s Ab have been found to disrupt neuronal function and to produce memory deficits prior to the appearance of large amyloid plaques or the occurrence of overt neuronal death. This observation is important because it suggests that early cognitive impairments in AD may precede extensive neurodegeneration and may thus be reversible. Understanding the molecular and signaling events elicited in neurons by oligomeric Ab that lead to memory deficits is therefore crucial to develop an effective therapeutic strategy. We have recently discovered that calcineurin, a phosphatase abundant in neurons and involved in negative modulation of synaptic plasticity and memory, plays a central role in mediating oligomeric Ab-induced cognitive deficits. We found that oliogomeric Ab induces calcineurin and that in cognitively-impaired but plaque-free transgenic mice overexpressing human Ab there is an up-regulation of calcineurin activity in the CNS. We further found that acute pharmacologic inhibition of calcineurin reverses cognitive deficits in these mice. Our most current research effort is thus to understand the molecular players downstream of oligomeric Ab/calcineurin and the relevance of calcineurin hyper-activation in AD human brains and other amyloid neurodegenerative diseases where amyloid oligomers are know to play a significant role.
- Thomas M.S., Zhang W.R., Jordan P.M., Saragovi H.U., Taglialatela G. (2005): Signaling pathways mediating a selective induction of nitric oxide synthase II by tumor necrosis factor alpha in nerve growth factor-responsive cells. J Neuroinflammation 2: 19.
- Portier B, Ferrari D, Taglialatela G (2006): Rapid assay for quantitative measurement of apoptosis in cultured cells and brain tissue. J Neurosci Meth, 155(1):134-42; E-pub ahead of print March 23, 2006.
- Portier B, Taglialatela G (2006): Bcl-2 localized at the nuclear compartment induces apoptosis after transient overexpression. J Biol Chem, 281(52):40493-502; E-pub ahead of print November 7, 2006.
- Karlnoski R, Wilcock D, Dickey C, Ronan V, Gordon MN, Zhang WR, Morgan D, Taglialatela G (2007): Up-Regulation of Bcl-2 in APP Transgenic Mice is Functionally Neuroprotective, Neurobiol Dis, 25(1):179-88; E-pub ahead of print October 25, 2006.
- Dineley K, Hogan D, Zhang W, Taglialatela G (2007): Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice. Neurobiol Learn Mem. 88(2):217-224.