Impact of corticoid receptors on Alzheimer's disease: a neuroendocrine perspective.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been strongly associated with changes in corticoid receptor function and HPA axis dysregulation. This review gives an overview of the complex role of GC and MC receptors in AD, especially how chronic exposure to elevated cortisol contributes to hippocampal degeneration, oxidative stress, and cognitive decline. Specific emphasis lies with cortisol, brought to the attention of neurotoxicity, and relates it to Cushing syndrome with chronic hyper-cortisolism simulating cognitive and structural impairments seen in AD. The impact of HPA axis over-activity in AD pathology is presented, demonstrating its contribution to neuro-inflammation and possible utilization as a biomarker for disease progression. This review further includes pharmacological strategies that modulate corticoid receptors for the reduction of GC-induced neurotoxicity and includes selective GR antagonists and MR agonists. Lifestyle modifications, which modulate HPA activity, are the other non-pharmacological approach to managing AD. Finally, novel drugs and interventions targeting the regulation of GC, anti-inflammatory pathways, as well as attenuation of oxidative stress are emerging strategies. Such a strategy implies that it is possible that receptor activity balance can delay or arrest AD progression.