Ceftriaxone's Multifaceted Neuroprotection in Parkinson's Disease: Preclinical Evidence and Implications for Drug Repurposing.

Ceftriaxone is a well-established broad-spectrum β-lactam antibiotic that has attracted wide attention in recent years because of its pleiotropic effect on nervous system diseases. Parkinson's disease (PD) is a common neurodegenerative disorder. At present, there is no cure, and most available treatments are symptomatic, offering limited efficacy and accompanied by side effects. The repurposing of ceftriaxone for PD has shown promising neuroprotective effects in preclinical studies, primarily through mechanisms such as regulating glutamate transporter expression, alleviating neuroinflammation, counteracting oxidative stress, and reducing dopaminergic neuron damage. Its molecular targets, pharmacokinetic characteristics, and safety profile have been increasingly elucidated. Some studies suggest that ceftriaxone may have synergistic effect with existing PD medications. Although current evidence is mostly preclinical and clinical translation still needs to be verified, the multi-target effects of ceftriaxone have opened a new direction for drug repurposing in PD. This paper aims to sort out the mechanism, existing evidence and future development prospect of ceftriaxone in PD, and provide theoretical reference for related basic and clinical research.