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Science 18 July 1997:
Vol. 277. no. 5324, pp. 373 - 376
DOI: 10.1126/science.277.5324.373
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Reports

Alternative Cleavage of Alzheimer-Associated Presenilins During Apoptosis by a Caspase-3 Family Protease

Tae-Wan Kim, Warren H. Pettingell, Yong-Keun Jung, Dora M. Kovacs, Rudolph E. Tanzi *

Most cases of early-onset familial Alzheimer's disease (FAD) are caused by mutations in the genes encoding the presenilin 1 (PS1) and PS2 proteins, both of which undergo regulated endoproteolytic processing. During apoptosis, PS1 and PS2 were shown to be cleaved at sites distal to their normal cleavage sites by a caspase-3 family protease. In cells expressing PS2 containing the asparagine-141 FAD mutant, the ratio of alternative to normal PS2 cleavage fragments was increased relative to wild-type PS2-expressing cells, suggesting a potential role for apoptosis-associated cleavage of presenilins in the pathogenesis of Alzheimer's disease.

T.-W. Kim, W. H. Pettingell, D. M. Kovacs, R. E. Tanzi, Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Y.-K. Jung, Department of Life Science, KwangJu Institute of Science and Technology, 572 Sangam-dong, Kwangsan-ku, KwangJu, Korea.
*   To whom correspondence should be addressed. E-mail: tanzi{at}helix.mgh.harvard.edu

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Arch Neurol 55, 294-296
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C. E. Finch and R. E. Tanzi (1997)
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R. N. Rosenberg (1997)
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Y. Zhang, H. Kornfeld, W. W. Cruikshank, S. Kim, C. C. Reardon, and D. M. Center (2001)
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