Endogenous glucocorticoids: role in the etiopathogenesis of Alzheimer's disease

Research output: Contribution to journalReview articlepeer-review

Abstract

Endogenous glucocorticoids (eGCs) are steroid hormones with a wide spectrum of physiological effects. However, enhanced basal eGCs levels have been observed in patients affected by Alzheimer's disease (AD) and they have been correlated with dysregulation of the hypothalamic-pituitary-adrenocortical axis, hippocampal degeneration and reduced cognitive/memory performance. Therefore, it has been proposed that elevated concentration of eGCs might have a role in AD pathogenesis. AD is the most common form of dementia, characterized by the pathological accumulation of two proteins: the Amyloid Beta (Aβ) and the microtubule-associated protein tau in the neurons of the hippocampus and prefrontal cortex. In particular, the hippocampus, the cerebral area involved in learning and memory, is the brain region more vulnerable to chronic eGCs exposure. Although clinical studies have failed to establish a direct causative link between eGCs e and AD pathogenesis, evidences from pre-clinical studies have shown that increased eGCs levels accelerate the formation of Aβ in AD animal models by promoting the amyloidogenic pathway, and in parallel by reducing Aβ clearance, through transcriptional mechanisms involving the Glucocorticoid receptors. Instead, the effects of stress on tau phosphorylation seem to be mainly mediated bv the corticotropin-releasing factor receptor (CRFR1) and independent from stress-induced eGCs elevation.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalNeuroendocrinology Letters
Volume38
Issue number1
Publication statusPublished - Feb 2017

Keywords

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Brain
  • Cognitive Dysfunction
  • Glucocorticoids
  • Hippocampus
  • Humans
  • Hypothalamo-Hypophyseal System
  • Memory Disorders
  • Phosphorylation
  • Pituitary-Adrenal System
  • Protein Aggregation, Pathological
  • Receptors, Corticotropin-Releasing Hormone
  • tau Proteins
  • Journal Article
  • Review

Fingerprint Dive into the research topics of 'Endogenous glucocorticoids: role in the etiopathogenesis of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this