In cerebrospinal fluid ER chaperones ERp57 and calreticulin bind beta-amyloid
| Autor: | Jordan L. Holtzman, Douglas Olson, W. Gibson Wood, Sheftel J. Cohen, Lisa M. Dunning, Richard R. Erickson, Robert A. Kratzke, Alan T. Davis |
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| Rok vydání: | 2005 |
| Předmět: |
Aging
Biophysics Protein Disulfide-Isomerases Endoplasmic Reticulum Biochemistry Cerebrospinal fluid β amyloid mental disorders Amyloid precursor protein Humans Isomerases Molecular Biology Heat-Shock Proteins Amyloid beta-Peptides biology Endoplasmic reticulum Cell Biology Membrane protein Carrier protein Unfolded protein response biology.protein Calreticulin Molecular Chaperones Protein Binding |
| Zdroj: | Biochemical and biophysical research communications. 332(1) |
| ISSN: | 0006-291X |
| Popis: | The β-amyloids (abetas) are the major components of the plaque observed in the brains of patients with Alzheimer’s disease. The conundrum is that although they are produced in everyone during the posttranslational processing in the endoplasmic reticulum (ER) of the amyloid precursor protein (APP), deposits are only observed in the elderly. Our work suggests that normals have a carrier protein(s) keeping them in solution. Based on immunoblotting studies of cerebrospinal fluid (CSF) from normals, we find that the bulk of the abetas are bound to the ER chaperones, ERp57 and calreticulin, suggesting that these may be carrier proteins which prevent aggregation of the abetas and that the deposits are due to faulty ER posttranslational processing of APP with the failure to form this complex. If membrane protein synthesis is similarly affected, it could explain the neuronal dysfunction characteristic of Alzheimer’s disease. |
| Databáze: | OpenAIRE |
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