PT  - JOURNAL ARTICLE
AU  - Atish Mukherjee
AU  - Eun-suk Song
AU  - Muthoni Kihiko-Ehmann
AU  - Jack P. Goodman, Jr
AU  - Jan  St. Pyrek
AU  - Steven Estus
AU  - Louis B. Hersh
TI  - Insulysin Hydrolyzes Amyloid β Peptides to Products That Are Neither Neurotoxic Nor Deposit on Amyloid Plaques
AID  - 10.1523/JNEUROSCI.20-23-08745.2000
DP  - 2000 Dec 01
TA  - The Journal of Neuroscience
PG  - 8745--8749
VI  - 20
IP  - 23
4099  - http://www.jneurosci.org/content/20/23/8745.short
4100  - http://www.jneurosci.org/content/20/23/8745.full
SO  - J. Neurosci.2000 Dec 01; 20
AB  - 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 Aβ1–40 and Aβ1–42by the recombinant enzyme was shown to initially occur at the His13-His14, His14-Gln15, and Phe19-Phe20 bonds. This was followed by a slower cleavage at the Lys28-Gly29, Val18-Phe19, and Phe20-Ala21 positions. None of the products appeared to be further metabolized by insulysin. Using a rat cortical cell system, the action of insulysin on Aβ1–40 and Aβ1–42 was shown to eliminate the neurotoxic effects of these peptides. Insulysin was further shown to prevent the deposition of Aβ1–40 onto 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.