- Selective mGlu3 metabotropic glutamate receptor ligands as new potential therapeutic agents in experimental models of parkinsonism.



Funding body
PRIN 2017
114.000 €

Departments and Centres



Department of Pharmaceutical Sciences


Working group

Mariagrazia Grilli
Fausto Chiazza
Valeria Bortolotto
Heather Bondi

Project duration

Start date
End date

Parkinson’s Disease (PD) is a chronic and progressive neurodegenerative disease with the main symptoms being loss of control over voluntary movements, as well as shaking and stiffness. The average age for emergence of the disease is around 60 years old, with a prevalence of 1-2% in the general population and 3-5% in people aged over 85.

The serious clinical effects of the disease are due to the gradual loss of dopaminergic neurons in the brain area known as ‘substantia nigra’ (black substance). So far, despite the availability of drugs such as Levo-DOPA and the dopaminergic agonists, treatment of this disease is exclusively limited to alleviation of symptoms. Within a few years, the loss of SN neurons inexorably leads to devastating effects on the autonomy and quality of life of patients and their families.

It is therefore necessary to identify new molecules which can act to prevent the progression of this neurodegenerative disease.

This project is supported by experimental findings that some glutamate receptors (mGlu3) located in the neuronal synapse area and glia play a protective role for SN neurons.

The specific goal of the project, which involves researchers in the medical, biological and chemistry fields, is to check whether pharmacological activation of mGlu3 receptors via new synthesis molecules can affect biochemical and ultra-structural alterations of Parkinson’s Disease and the neural inflammation linked to SN. According to the research hypothesis, this could occur via the release by non-neuronal cells (glial and neural stem cells) of protective factors and neurotrophins which not only prevent neurodegeneration but could also stimulate generation of neurons in SN.


UPO makes a specific contribution with the study of the effects of pharmacological modulation of mGlu3 receptors on the population of neural stem cells in SN (an area which is not neurogenic in normal physiological conditions) and their communication with astrocytes that can produce neuroprotective and pro-neurogen stimuli in other areas.


The project involves various research groups with certified experience in these receptors and the development of experimental in vitro and in vivo models for the study of Parkinson’s Disease. 
Università degli Studi of ROME "La Sapienza" (Prof. Ferdinando Nicoletti, Coordinator and one of the world’s leading experts in mGlu receptors)
Università degli Studi of PISA (Prof. Francesco Fornai)
Università degli Studi of ROMA "Tor Vergata" (Prof. Robert Giovanni Nisticò)
Università degli Studi of CATANIA (Prof. Maria Angela Sortino)
Università degli Studi of PALERMO (Dr. Virginia Spanò)