FINALIZZATA MIN SAL - Investigation of antiglutamatergic strategies for the neuroprotective therapy of juvenile Parkinson's disease - Resp. L. Murru (DSB.AD004.228)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Institute of neuroscience (IN)

Project manager

LUCA MURRU
Phone number: 02-50316973
Email: lc.murru@gmail.com

Abstract

Loss of function mutations in the gene PARK2 cause Autosomal Recessive Juvenile Parkinsonism (ARJP), aneurodegenerative disease characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta(SNc). No neuroprotective therapy exists; therapy development needs the identification/validation of molecular targets whose modulation blocks the toxic effects of PARK2 mutations. Evidence shows that PARK2 mutations in neurons upregulate function of kainate receptor (KAR), a ionotropic glutamate receptor expressed in many brain regions including SNc. KARs upregulation may induce an early synaptopathy leading to excitotoxicity and DA neuron death. This project aims at testing the hypothesis that pharmacological KAR inhibition rescues neurodegeneration in PARK2 pre-clinical models and at testing the hypothesis that KARs are upregulated in DA neurons of Parkinson's disease (PD) patients. This project may lead to the development of neuroprotective therapies.

Goals

-

Start date of activity

01/03/2019

Keywords

Parkinson's disease and other movement disorders, Kainate receptor, excitotoxicity

Last update: 22/05/2025