Nerve Growth Factor (NGF)

Scientific Activity

Our studies are focused on an Alzheimer-like molecular syndrome occurring in NGF target neurons.

A  wide range of experimental paradigms (neuronal cell lines, primary neuronal cultures, acute septo-hippocampal brain slices, transgenic animal models, human AD brain tissues and cerebrospinal fluid(CSF) samples are currently ongoing by the use of  protein biochemistry, recombinant DNA, immunohistochemistry light and electron microscopy. The lines of investigations are:

NGF-driven control of APP processing in central neurons.

The understanding of NGF/ TrkA mediated control of Amyloid Precursor Protein (APP) metabolism   is currently investigated by analyzing the possible direct interaction between these two membrane proteins and the direct posttranslational control of such interplay mediated by Shc protein. The role of the insulin hormone and of cholesterol metabolites (oxysterols) on NGF signaling and APP processing in the forebrain is also under investigation.

Tau as a necessary mediator in amyloid beta (Ab)-induced neurotoxicity.

NGF withdrawal of some target neurons is also followed by  N-terminal truncation of a 20-22 Kd peptide of tau protein. we found that this peptide is (i) neurotoxic in primary cultured neurons; (ii) present in cellular and animal AD models in correlation with neurotrophin withdrawal; (iii) enriched in human mitochondria from AD synaptosomes and associated to synaptic disarrangement, Ab oligomers load and structural and functional impairment of mitochondria; iv) detected in CSF from living patients affected by tauopathies, providing  a novel clinical  biomarker of  severity and progression of cognitive decline.

The physiopathological role of neuropeptides involved in AD.

The neuroprotective and antiamiloidogenic role of Substance P in the neuroinflammatory processes related to Ab toxicity, the study of potential anti-inflammatory drugs, and the signalling pathways stimulated by painless NGF  are under current investigation

Early synaptic events following NGF withdrawal as trigger of a dying  back mechanism.

We have developed an in vitro model of septal NGF-dependent neurons which survive in vitro only in the presence of this neurotrophin  and undergo a series of early (hours)synaptic events following its withdrawal. We are particularly focusing on pre and postsynaptic proteins potentially involved in these events and in the subsequent amyloidogenic processing and  neuronal death occurring after NGF withdrawal.