Role of Protease Inhibitor for Senile Plaque Formation

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1. Intracerebroventricular injection of protease inhibitor, leupeptin, and E-64, induced swelling and degeneration of neuronal axon in injected sites, which were closely similar to the neuronal changes in the neuritic plaques of Alzheimer's diseae. Alpha-1-antichymotrypsin, the protease inhibitor, which was demonstrated immunohistochemically in the neuritic plaques, caused characteristic neuroaxonal changes in the spinal cord in rats.2. Leupeptin showed stimulating and toxic effects of proliferation of axons in the cultured neuronal cells.3. Intracerebroventricular administration of leupeptin, protease inhibitor, caused a significant learning impairment in passive avoidance test in rats.Neuroaxonal changes, induced by protease inhibitor, were closely similar to the axonal changes in the vicinity of amyloid core in neuritic plaques. The neuronal changes by leupeptin administration caused a learning impairment in animals. Results of the present studies indicated the importance of protease inhibitor to from a specific neuritic changes in neuritic plaques in Alzheimer's disease.