Abstract
<title>Abstract</title> <p>Background The receptor for advanced glycation end products (RAGE) plays a crucial role in mediating oxidative stress and neuroinflammation in Parkinson’s disease. FPS-ZM1, a selective RAGE inhibitor, shows neuroprotective potential but is limited by poor brain availability. Liposomal delivery systems may enhance its stability and penetration across the blood–brain barrier. Objective This study aimed to evaluate the neuroprotective efficacy of liposomal FP-1 peptide in a rotenone-induced Parkinsonian rat model. Methods Parkinson-like neurodegeneration was induced in Wistar rats using rotenone (0.5 mg/kg, s.c.) for 21 days. Liposomal FP-1 peptide (1 mg/kg, i.p.) and liposomal L-DOPA/Carbidopa (10/2.5 mg/kg, i.p.) were administered concurrently. Behavioral performance was assessed using cylinder, pole, and gait tests. Biochemical analyses included oxidative stress markers (MDA, GSH, SOD, and catalase) and neuroinflammatory cytokines (TNF-α, IL-6). Results Rotenone administration produced significant motor impairment, oxidative stress, and increased inflammatory cytokines. Treatment with liposomal FP-1 peptide markedly improved motor function, reduced lipid peroxidation and protein oxidation, restored antioxidant defenses, and suppressed inflammatory mediators. Liposomal L-DOPA/Carbidopa showed strong symptomatic improvement, while liposomal FP-1 demonstrated substantial neuroprotective effects. Conclusion Liposomal FP-1 peptide effectively attenuates oxidative stress and neuroinflammation, leading to improved behavioral and biochemical outcomes. These findings highlight its potential as a promising therapeutic strategy for Parkinson’s disease.</p>