| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
Beta-Amyloid protein, the primary pathogenic agent of Alzheimer disease, accumulates in the extracellular space in the brain and induces the degeneration of neurons. We have previously clarified that extracellularly applied beta-amyloid protein aggregates cytoskeletal actin and, as a result, impairs axonal transport (an important neuronal function responsible for transport of materials inside the neuronal cells). The purpose of the present study is to clarify how extracellular beta-amyloid protein aggregates intracellular actin. The present results are as follows. In cultured rat hippocampal neurons, 1) video-enhanced microscopy revealed that beta-amyloid protein progressively and irreversively inhibited anterograde and retrograde axonal transport, 2) beta-amyloid protein changed neurite morphology such as a reduction in neurite width, 3) impairment of axonal transport by beta-amyloid protein was blocked by actin depolymerizing agent and mimicked by actin polymerizing agent, 4) fluorescence staining and fluorescent microscopy observation revealed that beta-amyloid protein was strongly attached to the cell and aggregated intracellular actin, 5) beta-amyloid protein was bound to G-actin (monomer globular actin) and aggregated G-actin. These results, considering the previous others' reports indicating that beta-amyloid protein interacts with cell membrane, indicate that beta-amyloid protein possibly inserts into the cell membrane, directly interacts with intracellular actin, and aggregates actin. As a result, beta-amyloid protein causes impairment of axonal transport.
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