Drug repurposing of dimethyl fumarate in Parkinson's disease: a promising disease-modifying strategy.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and pathological aggregation of a-synuclein. Despite advancements in symptomatic treatment, there is a critical unmet need for disease-modifying therapies capable of halting or slowing disease progression. Drug repurposing offers an efficient, cost-effective strategy to identify new treatments by leveraging the established safety and pharmacokinetic profiles of existing compounds. Dimethyl fumarate (DMF), an FDA-approved drug for multiple sclerosis and psoriasis, has recently emerged as a promising neuroprotective agent in PD research. Preclinical studies consistently demonstrate that DMF exerts beneficial effects in both in vitro and in vivo PD models, primarily via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Through this mechanism, DMF counters oxidative stress, reduces neuroinflammation, promotes mitochondrial quality control, and impedes pathological protein aggregation. These biological effects translate into the preservation of dopaminergic neurons and improvements in motor behavior in animal models. Although direct clinical evidence of DMF's efficacy in PD patients is currently very limited, early mechanistic human studies provide indirect support for the targeting of the Nrf2 pathway in PD. Furthermore, DMF's neuroprotective properties extend to other neurodegenerative diseases, underscoring its broader therapeutic potential. In conclusion, the strong preclinical foundation, combined with an established clinical safety record, makes DMF an attractive candidate for repurposing as a disease-modifying therapy for PD. Future clinical trials will be essential to validate these preclinical promises and define DMF's role in the management of PD.

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