Fumaric Acid Esters Attenuate Degeneration and Promote Functional Recovery Following Parkinson’s Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic nigrostriatal neurons and loss of substantia nigra. Fumaric acid esters (FAEs) display immunomodulatory and anti-inflammatory properties. Recent studies showed that treatment with FAEs significantly reduces leukocyte infiltration in experimental autoimmune encephalomyelitis and colitis and also activates the Nrf2 antioxidant response pathway. The aim of the present study was to evaluate the potential effects of dimethyl fumarate (DMF) in a mouse model of PD. Mice received four injections of the dopaminergic neurotoxin MPTP, starting 24 h after the first administration of MPTP, animals received DMF (10-30-100 mg/kg ip) daily for 7 days. On the 8th days, brains were processed for future analysis. Treatments with DMF significantly increased the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and reduced α-synuclein; moreover, DMF treatment significantly reduced pro-inflammatory markers such as NFκB, COX-2 and nitrosative stress and exerts protective effects enhancing recovery of motor function. The results of the present study clearly showed that DMF exerts its neuroprotective effects possibly by reducing the neuroinflammation and activating the Nrf2 antioxidant response pathway. DMF may constitute a promising therapeutic target for the treatment of neurodegenerative diseases such as PD.