TY - JOUR
T1 - Insulysin hydrolyzes amyloid β peptides to products that are neither neurotoxic nor deposit on amyloid plaques
AU - Mukherjee, A.
AU - Song, E. S.
AU - Kihiko-Ehmann, M.
AU - Goodman, Jr
AU - St. Pyrek, J.
AU - Estus, S.
AU - Hersh, L. B.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - 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 Aβ(1-40) and Aβ(1-42) by the recombinant enzyme was shown to initially occur at the His13-His(14), His(14)-Gln(15), and Phe(19)-Phe(20) bonds. This was followed by a slower cleavage at the Lys(28)-Gly(29), Val(18)-Phe(19), and Phe(20)-Ala(21) positions. None of the products appeared to be further metabolized by insulysin. Using a rat cortical cell system, the action of insulysin on Aβ(1-40) and Aβ(1-42) was shown to eliminate the neurotoxic effects of these peptides. Insulysin was further shown to prevent the deposition of Aβ(1-40) 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.
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 Aβ(1-40) and Aβ(1-42) by the recombinant enzyme was shown to initially occur at the His13-His(14), His(14)-Gln(15), and Phe(19)-Phe(20) bonds. This was followed by a slower cleavage at the Lys(28)-Gly(29), Val(18)-Phe(19), and Phe(20)-Ala(21) positions. None of the products appeared to be further metabolized by insulysin. Using a rat cortical cell system, the action of insulysin on Aβ(1-40) and Aβ(1-42) was shown to eliminate the neurotoxic effects of these peptides. Insulysin was further shown to prevent the deposition of Aβ(1-40) 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.
KW - Amyloid peptide metabolism
KW - Aβ cleavage
KW - Aβ deposition
KW - Aβ neurotoxicity
KW - Insulysin
KW - Metallopeptidase
UR - http://www.scopus.com/inward/record.url?scp=0034551718&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034551718&partnerID=8YFLogxK
U2 - 10.1523/jneurosci.20-23-08745.2000
DO - 10.1523/jneurosci.20-23-08745.2000
M3 - Article
C2 - 11102481
AN - SCOPUS:0034551718
SN - 0270-6474
VL - 20
SP - 8745
EP - 8749
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 23
ER -