The role of lysosomal proteinases and estradiol in neurodegeneration induced by beta-amyloid.

Activation of lysosomal degradation process in nervous tissue may be neuroprotective. One of the factors that may influence on expression of lysosomal proteinases is the sex hormone, estradiol (E2). In this regard the expression of lysosomal proteinases after intracerebral injection of beta-amyloid peptide (Aβ) was investigated as well as the neuroprotective effect of E2 in Aβ-induced neurodegeneration. Intracerebral injection of Aβ was shown to cause the significant increase in expression of cathepsin D in rat hippocampus and cerebral cortex. On the background of Aβ intoxication, E2 treatment resulted in further increase in cathepsin D gene expression in hippocampus region and in its lowering to the control level in cerebral cortex. It was demonstrated for the first time that neuroprotective effect of E2 may be mediated by cathepsin D up-regulation.