ABSTRACT
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and pathological changes, including amyloid-beta accumulation, neuroinflammation, and synaptic dysfunction. N-acetyl glucosamine (GlcNAc), a naturally occurring amino sugar, has emerged as a potential therapeutic candidate for AD due to its neuroprotective properties. This study aimed to investigate the effects of GlcNAc on key pathways implicated in AD pathogenesis and to elucidate its mechanisms of action in a scopolamine-induced mouse model. In this study, mice were subjected to preventive and curative treatment regimens with varying doses of GlcNAc (100, 200, and 400 mg/kg) or donepezil (a standard AD therapeutic). The expression levels of BACE1, APOE4, and potassium channels were evaluated in the cerebellum and cortex using appropriate molecular techniques. The results demonstrated that GlcNAc administration significantly modulated BACE1 expression, APOE4 levels, and potassium channel dysregulation in both preventive and curative settings. Notably, the neuroprotective effects of GlcNAc exhibited dose-dependent and brain region-specific responses, with higher doses (200 and 400 mg/kg) generally more effective than lower doses. Interestingly, the therapeutic effects of GlcNAc were comparable or superior to those of donepezil, suggesting distinct mechanisms of action. Furthermore, GlcNAc treatment led to a significant upregulation of APOE4 expression, implying its potential to improve cholesterol distribution and synaptic remodeling processes impaired in AD. Additionally, GlcNAc effectively mitigated potassium channel dysregulation, which is associated with neuronal excitability alterations and cognitive impairment in AD. In conclusion, this study provides compelling evidence for the neuroprotective effects of GlcNAc in an AD mouse model. GlcNAc modulated multiple key pathways implicated in AD pathogenesis, including amyloidogenesis, neuroinflammation, and synaptic dysfunction, suggesting its potential as a novel therapeutic candidate for AD. These findings contribute to the growing body of knowledge on the therapeutic utility of GlcNAc and pave the way for further investigations into its underlying mechanisms, dose optimization, and clinical efficacy evaluation. Keywords: Alzheimer’s disease (AD), Neurodegenerative disorder, Cognitive decline, N-acetyl glucosamine (GlcNAc), Neuroprotective properties, Amyloid-beta accumulation, Synaptic dysfunction, BACE1 expression, APOE4 levels, Therapeutic candidate.
