The interaction of neurotrophins and
their tyrosine kinase receptors (trks) is
essential for differentiation and survival
of brain cells. In Alzheimer’s disease
(AD), the number of neurotrophins and
receptors is markedly decreased. The
cause of this reduction is unclear, but
the role of b-amyloid (Ab) seems central
in understandingthe mechanisms controllingneur
otrophin and trk expression.
In the study reported here, we exposed
SHSY5Y neuroblastoma cells to Ab or
hydrogen peroxide (H2O2) and measured
the expression of trk-A and p75 at the
protein and molecular levels. Both Ab
and H2O2 induced oxidative stress (measured
by a decrease in cellular glutathione),
which decreased trk-A levels and
increased p75 levels, decreased messenger
RNA (mRNA) levels of both receptors,
and increased nerve growth
factor (NGF) secretion. Pretreatment of
cells with the antioxidant melatonin returned
levels of protein expression,
mRNA, and NGF secretion to normal.
These results are significant, as they
can help in the planningand implementation
of AD treatment strategies involvingneur
otrophins.