Glycyrrhizic Acid Attenuates Aβ42-Induced Neurodegeneration Through Coordinated Regulation of Oxidative Stress, Synaptic Markers, and Key Alzheimer’s Signaling Pathways

Alzheimer’s disease (AD) is a catastrophic neurodegenerative disorder marked by progressive decline of cognitive function, memory loss, and neuronal death. Its pathology is characterized by the formation of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles from tau hyperphosphorylation. Despite extensive research, current treatments are limited to symptomatic relief and are associated with significant side effects. This accentuates the critical need for alternative therapeutic strategies with potent neuroprotective effects and minimal toxicity. This study investigates the neuroprotective potential of glycyrrhizic acid, as the precise molecular mechanisms by which it might improve AD pathology remain poorly understood. Using an Aβ42-induced IMR-32 cell model of AD, our research revealed that Aβ42 treatment caused significant protein alterations associated with AD pathology, mitochondrial dysfunction, cell cycle re-entry, and synaptic activity. Co-treatment with glycyrrhizic acid not only restored these protein levels, but also mitigated the hyperactivation of several key signaling pathways and rescued neurons from apoptosis. These findings suggest that glycyrrhizic acid exerts neuroprotective effects by preventing mitochondrial dysfunction and apoptosis via modulation of critical signaling pathways. This study provides strong evidence for glycyrrhizic acid’s neuroprotective properties in AD, paving the way for further research into its potential as a promising therapeutic agent for Alzheimer’s disease.