Preventive effect of a garlic compound on astrocyte-mediated neuroinflammation in Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuron loss and resultant severe motor dysfunction. While current treatments primarily focus on maintaining dopamine levels, effective targeting of neuroinflammation, an important driver of disease progression, remains an unmet need. This study investigates the neuroprotective potential of BMDA (BMDA(N-benzyl-N-methyldecan-1-amine)), a natural compound derived from garlic with strong anti-inflammatory properties, using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced mouse model of PD. Behavioral assessments, immunohistochemistry, and dopamine analysis showed that BMDA effectively reduced neuroinflammation and preserved dopaminergic neurons. In vitro studies showed that BMDA significantly suppressed inflammatory markers and reduced astrocyte activation in MPP⁺-induced primary cultured astrocytes, and real-time PCR confirmed that BMDA attenuated proinflammatory cytokines and chemokines. Further mechanistic studies showed that BMDA inhibited the p-p65 and p-ERK signaling pathways, which underlie astrocyte-mediated neuroinflammation. These findings suggest that BMDA should be considered a therapeutic candidate for PD that targets neuroinflammation.