Neurotrophic factors, and especially the neurotrophins, are proteins known to play a key role in neuronal repair, maintenance and differentiation as well as to model our neuronal circuitry. Therefore, neurotrophins are essential to our ability to move, feel and think. The primary focus of Dr. Mocchetti's research program at Georgetown University is to study the neurobiology of the neurotrophins. The ultimate goal of such program is to use these proteins as potential biotherapies for human neurological disorders, such as Alzheimer's and Parkinson's diseases, stroke, trauma and AIDS dementia. Specifically, Dr. Mocchetti’s group is characterizing the neuroprotective effects of a major neurotrophin, Brain-Derived Neurotrophic Factor (BDNF). Using neuronal cultures, viral vectors and mutant mice, they have recently demonstrated that BDNF reduces neuronal cell death evoked by HIV-1 proteins, most likely by down-regulating chemokine receptors responsible for mediating viral neurotoxicity.  Based on these results, Dr. Mocchetti's group is currently studying synthetic compounds that mimic the neurotrophic effect of BDNF while being able to cross the blood brain barrier (BBB).  Using transfected cell lines and technique probing different signal transduction pathways, his group has recently demonstrated that gangliosides, compounds able to cross the BBB, indeed mimic the neurotrophic effects of the neurotrophins. These exciting results raise a legitimate hope that gangliosides and potentially other compounds yet to be identified could be used as therapeutic tools in neurodegenerative diseases. 


Selected Publications:

• Shimoji M, Pagan F, Healton EB, Mocchetti I. CXCR4 and CXCL12 Expression is Increased in the Nigro-Striatal System of Parkinson's Disease. Neurotox Res. 2009