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Oxidative stress modulates tyrosine kinase receptor A and p75 receptor (low-affinity nerve growth factor receptor)

G Olivieri1, U Otten, F Meier

  • 1Neurobiology Laboratory, Psychiatric University Hospital, Basel, Switzerland. fianfranco.olivieri@pukbasel.ch

Neurology & Clinical Neurophysiology : NCN
|May 25, 2002
PubMed

Insights

Alzheimer's disease (AD) involves reduced neurotrophins. Beta-amyloid and oxidative stress decrease key receptors (trk-A) and increase others (p75), but melatonin may restore balance, offering potential AD treatment insights.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Neurotrophins and their tyrosine kinase receptors (trks) are vital for brain cell survival and differentiation.
  • Alzheimer's disease (AD) is characterized by decreased neurotrophin and trk levels, with beta-amyloid (Abeta) implicated in this reduction.
  • Understanding the mechanisms controlling neurotrophin and trk expression is crucial for AD research.

Purpose of the Study:

  • To investigate the impact of beta-amyloid (Abeta) and oxidative stress on neurotrophin receptor expression in neuronal cells.
  • To determine the role of oxidative stress in modulating trk-A and p75 receptor levels and nerve growth factor (NGF) secretion.
  • To evaluate the neuroprotective potential of melatonin against Abeta-induced changes in neuronal cells.

Main Methods:

  • SHSY5Y neuroblastoma cells were exposed to beta-amyloid (Abeta) or hydrogen peroxide (H(2)O(2)) to induce oxidative stress.
  • Expression levels of trk-A and p75 receptors were measured at both protein and molecular (mRNA) levels.
  • Cellular glutathione levels were assessed to quantify oxidative stress.
  • Nerve growth factor (NGF) secretion was measured.
  • The effect of melatonin pretreatment on these parameters was evaluated.

Main Results:

  • Both Abeta and H(2)O(2) induced oxidative stress, evidenced by decreased cellular glutathione.
  • Oxidative stress led to reduced trk-A protein and mRNA levels and increased p75 protein and mRNA levels.
  • Nerve growth factor (NGF) secretion was elevated under oxidative stress conditions.
  • Pretreatment with the antioxidant melatonin normalized the expression levels of trk-A, p75, and NGF secretion.

Conclusions:

  • Beta-amyloid and oxidative stress significantly alter neurotrophin receptor expression in neuronal cells, potentially contributing to Alzheimer's disease pathology.
  • Melatonin, an antioxidant, demonstrates a protective effect by reversing these detrimental changes, suggesting its therapeutic potential in AD.
  • These findings provide a basis for developing AD treatment strategies targeting neurotrophin pathways and oxidative stress.

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