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Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene

R Ghidoni1, L Gasparini, A Alberici

  • 1Scientific Institute IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Italy.

Journal of Neural Transmission (Vienna, Austria : 1996)
|August 26, 2003
PubMed

Insights

Alzheimer's Disease (AD) involves energy metabolism defects. Mitochondrial dysfunction, induced by inhibiting energy metabolism, down-regulates presenilin 2 (PS2) gene expression, suggesting redox imbalance modulates AD pathogenesis.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Defects in cellular energy metabolism and oxidative stress are implicated in Alzheimer's Disease (AD) pathogenesis.
  • Reduced presenilin 2 (PS2) mRNA levels are observed in affected brain regions in sporadic AD.
  • Mitochondrial dysfunction is a potential factor influencing PS2 gene expression in AD.

Purpose of the Study:

  • To investigate the link between mitochondrial dysfunction and PS2 gene expression.
  • To determine if inhibiting energy metabolism affects PS2 gene expression.
  • To explore the role of cellular redox homeostasis in modulating PS2 expression.

Main Methods:

  • Inhibition of cellular energy metabolism using sodium azide.
  • Analysis of PS2 gene promoter activity.
  • Assessment of transcription factor activity sensitive to cellular redox status.
  • Evaluation of the effect of antioxidants on PS2 expression.

Main Results:

  • Sodium azide treatment significantly down-regulated PS2 gene expression by altering promoter activity.
  • The observed effect was not attributable to known redox-sensitive transcription factors.
  • Co-administration of an antioxidant completely reversed the azide-induced down-regulation of PS2 expression.

Conclusions:

  • Mitochondrial dysfunction, through the inhibition of energy metabolism, directly impacts PS2 gene expression.
  • Cellular redox homeostasis imbalance is a key modulator of PS2 gene expression.
  • These findings provide insights into the molecular mechanisms underlying Alzheimer's Disease pathogenesis.

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