Targeting abnormal signalling in experimental Parkinsonism and L-DOPA-induced dyskinesia

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The Fisone Laboratory studies signal transduction mechanisms involved in neurodegenerative and neuropsychiatric disorders, such as Parkinson’s disease, schizophrenia and drug addiction. They have been particularly interested in the study of dopamine transmission, which is profoundly affected in all these conditions.

Their final goal is to identify molecular changes, which may represent novel targets for therapeutic interventions. Methodology is based on a combination of molecular biological, biochemical and behavioral techniques. Disease modelling coupled to cell-targeted expression of fluorescent proteins is used to investigate abnormal signaling and gene expression at the level of discrete groups of neurons. In parallel, specific signaling components are studied at the biochemical and behavioral level using pharma­cological tools, or by manipulating their expression both systemically and in a cell-specific manner. Using these strategies we have characterized key molecular events involved in the effects of various classes of psychoactive drugs. They have also identified abnormalities in signal transduction affecting distinct neuronal populations and underlying the severe motor complications, or dyskinesia, caused by prolonged administration of L-DOPA to parkinsonian patients. More recently, they have started to investigate the mechanisms at the basis of non-motor symptoms of PD, which include cognitive impairment and neuropsychiatric conditions, such as depression and anxiety.

They are also studying the effects of typical and atypical antipsychotic drugs on signal transduction processes in various brain regions.