Loss Of Fragile X Mental Retardation Protein (Fmrp) Precedes Lewy Pathology In Parkinson'S Disease

Objective: Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of a-synuclein-containing (a-syn) neuronal protein aggregates. Although the exact mechanism of a-syn-mediated cell death remains elusive, recent research suggests that a-syn-induced alterations in neuronal excitability contribute to cell death in PD. Because the Fragile X Mental Retardation Protein (FMRP) controls the expression and function of numerous neuronal genes related to neuronal excitability and synaptic function, we here investigated the role of FMRP in a-syn-associated pathological changes.