Parkinson's disease (PD) affects 1.2 million people in Europe[1]. Ten% of PD cases are due to genetic mutations and 90% are idiopathic[2]. No neuroprotective therapy exists. Since synaptic dysfunction is a major contributor to the death of dopamine (DA) neurons in PD[3,4], synapses can provide druggable targets for neuroprotection. The kainate receptor (KAR) is a glutamate receptor expressed in many synapses including the glutamatergic synapse to nigral DA neurons[5,6]. Evidence suggests that KAR antagonism rescues disease features in a genetic model of juvenile PD[7] (see preliminary data), raising the possibility that drugs acting on KAR may exert neuroprotective activity also in other PD forms. This project will test whether KAR antagonism rescues DA neuron synaptopathy and viability in genetic and/or idiopathic PD. Since ageing and PD share detrimental mechanisms[8,9], this project will also compare synaptopathy occurring in human DA neurons during aging and PD.
Targeting synapse dysfunction in Parkinson's disease
Morari M
2020
Abstract
Parkinson's disease (PD) affects 1.2 million people in Europe[1]. Ten% of PD cases are due to genetic mutations and 90% are idiopathic[2]. No neuroprotective therapy exists. Since synaptic dysfunction is a major contributor to the death of dopamine (DA) neurons in PD[3,4], synapses can provide druggable targets for neuroprotection. The kainate receptor (KAR) is a glutamate receptor expressed in many synapses including the glutamatergic synapse to nigral DA neurons[5,6]. Evidence suggests that KAR antagonism rescues disease features in a genetic model of juvenile PD[7] (see preliminary data), raising the possibility that drugs acting on KAR may exert neuroprotective activity also in other PD forms. This project will test whether KAR antagonism rescues DA neuron synaptopathy and viability in genetic and/or idiopathic PD. Since ageing and PD share detrimental mechanisms[8,9], this project will also compare synaptopathy occurring in human DA neurons during aging and PD.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
