The Neuroprotective Effects of Agmatine on Parkinson's Disease: Focus on Oxidative Stress, Inflammation and Molecular Mechanisms

Agmatine (AGM), a naturally occurring polyamine derived from L-arginine, has shown significant potential for neuroprotection in Parkinson's Disease (PD) due to its multifaceted biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects. This review explores the therapeutic potential of AGM in treating PD, focusing on its neuroprotective mechanisms and evidence from preclinical studies. AGM has been demonstrated to mitigate the neurotoxic effects of rotenone (ROT) by improving motor function, reducing oxidative stress markers, and decreasing levels of pro-inflammatory cytokines in animal models. Additionally, AGM protects against the loss of TH + neurons, crucial for dopamine synthesis. The neuroprotective properties of AGM are attributed to its ability to modulate several key pathways implicated in PD pathogenesis, such as inhibition of NMDA receptors, activation of Nrf2, and suppression of the HMGB1/ RAGE/ TLR4/ MyD88/ NF-κB signaling cascade. Furthermore, the potential of agmatine to promote neurorestoration is highlighted by its role in enhancing neuroplasticity elements such as CREB, BDNF, and ERK1/2. This review highlights agmatine's promising therapeutic potential in PD management, suggesting that it could offer both symptomatic relief and neuroprotective benefits, thereby modifying the disease course and improving the quality of life for patients. Further research is warranted to translate these preclinical findings into clinical applications.