Advanced glycation end products contribute to amyloidosis in Alzheimer disease
| Autor: | J. M. Glendening, Helen Vlassara, Keshab Bhattacharya, Michael P. Vitek, A. Cerami, Kirk R. Manogue, Richard Bucala, Edward G. Stopa |
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| Rok vydání: | 1994 |
| Předmět: |
chemistry.chemical_classification
Glycosylation Multidisciplinary Amyloid Amyloidosis Brain Enzyme-Linked Immunosorbent Assay Peptide medicine.disease Turn (biochemistry) Kinetics chemistry.chemical_compound Glucose chemistry Biochemistry Alzheimer Disease Glycation In vivo medicine Humans Thioflavin Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 91:4766-4770 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.91.11.4766 |
| Popis: | Alzheimer disease (AD) is characterized by deposits of an aggregated 42-amino-acid beta-amyloid peptide (beta AP) in the brain and cerebrovasculature. After a concentration-dependent lag period during in vitro incubations, soluble preparations of synthetic beta AP slowly form fibrillar aggregates that resemble natural amyloid and are measurable by sedimentation and thioflavin T-based fluorescence. Aggregation of soluble beta AP in these in vitro assays is enhanced by addition of small amounts of pre-aggregated beta-amyloid "seed" material. We also have prepared these seeds by using a naturally occurring reaction between glucose and protein amino groups resulting in the formation of advanced "glycosylation" end products (AGEs) which chemically crosslink proteins. AGE-modified beta AP-nucleation seeds further accelerated aggregation of soluble beta AP compared to non-modified "seed" material. Over time, nonenzymatic advanced glycation also results in the gradual accumulation of a set of posttranslational covalent adducts on long-lived proteins in vivo. In a standardized competitive ELISA, plaque fractions of AD brains were found to contain about 3-fold more AGE adducts per mg of protein than preparations from healthy, age-matched controls. These results suggest that the in vivo half-life of beta-amyloid is prolonged in AD, resulting in greater accumulation of AGE modifications which in turn may act to promote accumulation of additional amyloid. |
| Databáze: | OpenAIRE |
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