PRIN 2017 "Targeting early synaptic dysfunctions induced by alpha-synuclein as a novel therapeutic approach in Parkinson's disease" (DSB.AD004.266)

Thematic area

Biomedical sciences

Project area

Structure responsible for the research project

Istituto di Biochimica e Biologia Cellulare (IBBC)

Project manager

ELVIRA DE LEONIBUS
Phone number: 0690091
Email: elvira.deleonibus@cnr.it

Abstract

Levodopa is still considered the gold-standard therapy in Parkinson's disease (PD). However, the long-term use of this dopamine precursor is complicated by highly disabling levodopa-induced dyskinesias (LIDs). Altered striatal glutamatergic transmission and plasticity together with dopaminergic denervation are crucial for LIDs occurrence. Alpha-synuclein (a-syn) and leucine-rich repeat kinase 2 (LRRK2) play a role in both genetic and sporadic forms of PD, acting at pre- and post-synaptic sites to regulate movement and striatal synaptic activity. Nevertheless, a direct involvement of a-syn and LRRK2 in the pathophysiology of LIDs is unclear. Our project aims at identifying the role of these proteins in LIDs with a multidisciplinary approach combining behavioural, electrophysiological and molecular approaches in experimental models of PD. Moreover, cerebrospinal fluid (CSF) from a well characterized cohort of PD patients will be analyzed for a-syn and LRRK2 status and tested in vitro to clarify the role of these proteins on synaptic and molecular features related to LIDs. Finally, we will test drugs selectively targeting a-syn and LRRK2 to assess potential beneficial effects on LIDs

Start date of activity

30/08/2019

Keywords

Alpha-synuclein, dyskinesias, leucine-rich repeat kinase 2 (LRRK2)

Last update: 08/06/2025