Insulysin Hydrolyzes Amyloid β Peptides to Products That Are Neither Neurotoxic Nor Deposit on Amyloid Plaques
| Autor: | Jan St. Pyrek, Atish Mukherjee, Muthoni Kihiko-Ehmann, Louis B. Hersh, Eun-Suk Song, Jack P. Goodman, Steven Estus |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Amyloid
Cell Survival Plaque Amyloid Cleavage (embryo) Insulysin Recombinant enzyme law.invention Hydrolysis Cortical cell law mental disorders Animals ARTICLE Cells Cultured Chromatography High Pressure Liquid Neurons Amyloid beta-Peptides Chemistry General Neuroscience Peptide Fragments Recombinant Proteins Amyloid β peptide Rats Neuroprotective Agents Biochemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Recombinant DNA |
| Zdroj: | The Journal of Neuroscience. 20:8745-8749 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.20-23-08745.2000 |
| Popis: | Insulysin (EC. 3.4.22.11) has been implicated in the clearance of β amyloid peptides through hydrolytic cleavage. To further study the action of insulysin on Aβ peptides recombinant rat insulysin was used. Cleavage of both Aβ1–40and Aβ1–42by the recombinant enzyme was shown to initially occur at the His13-His14, His14-Gln15, and Phe19-Phe20bonds. This was followed by a slower cleavage at the Lys28-Gly29, Val18-Phe19, and Phe20-Ala21positions. None of the products appeared to be further metabolized by insulysin. Using a rat cortical cell system, the action of insulysin on Aβ1–40and Aβ1–42was shown to eliminate the neurotoxic effects of these peptides. Insulysin was further shown to prevent the deposition of Aβ1–40onto a synthetic amyloid. Taken together these results suggest that the use of insulysin to hydrolyze Aβ peptides represents an alternative gene therapeutic approach to the treatment of Alzheimer's disease. |
| Databáze: | OpenAIRE |
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