Analysis of β-Amyloid Peptide -Binding Proteins in Microglial Cell

ABSTRACT

Alzheimer’s disease is the most common form of dementia in the elderly. Although β-amyloid peptide (Aβ) has been considered major cause of Alzheimer pathology, molecular and cellular mechanisms of the disease development of Alzheimer have not been clarified yet. Presently Aβ has been considered to induce neural cell death by direct penetration of aggregated form or indirect cell death by inflammatory responses induced by Aβ-activated microglia. In order to understand Aβ induced microglial activation, we searched the proteins which bind to Aβ in activated microglial cell line. We stimulated Ra2 microglial cell line with Aβ. Activated Ra2 cells were immunoprecipitated with anti- Aβ and run the gel. Membrane was silver stained and bands were cut and digested with enzyme. They were analyzed by LC/MS/MS. We found that several proteins including myosin 9 and actin bound to Aβ. By the addition of Aβ, actin binding was enhanced and other proteins including IQGAP1, Plectin strongly bound to Aβ. These results indicate that Aβ binds to the proteins belonging to cellular cytoskeletal system.

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