We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss.
- Authors
Campbell, William A.; Hongwei Yang; Zetterberg, Henrik; Baulac, Stéphanie; Sears, Jacqueline A.; Tianming Liu; Wong, Stephen T. C.; Zhong, Tao P.; Weiming Xia
- Abstract
γ-Secretase cleavage, mediated by a complex of presenilin, presenilin enhancer (Pen-2), nicastrin, and Aph-1, is the final proteolytic step in generating amyloid β protein found in brains of Alzheimer's disease patients and Notch intracellular domain critical for proper neuronal development. Here, we employ the zebrafish model to study the role of Pen-2 in neuronal survival. We found that (i) knockdown of Pen-2 using antisense morpholino led to a reduction of islet-1 positive neurons, (ii) Notch signaling was reduced in embryos lacking Pen-2 or other γ-secretase components, (iii) neuronal loss in Pen-2 knockdown embryos is not as a result of a lack of neuronal precursor cells or cell proliferation, (iv) absence of Pen-2 caused massive apoptosis in the whole animal, which could be suppressed by simultaneous knockdown of the tumor suppressor p53, (v) loss of islet-1 or acetylated tubulin positive neurons in Pen-2 knockdown embryos could be partially rescued by knockdown of p53. Our results demonstrate that knockdown of Pen-2 directly induces a p53-dependent apoptotic pathway that contributes to neuronal loss and suggest that Pen-2 plays an important role in promoting neuronal cell survival and protecting from apoptosis in vivo.
- Subjects
ZEBRA danio; ALZHEIMER'S disease; PRESENILINS; P53 protein; APOPTOSIS; NEURONS; CELL death
- Publication
Journal of Neurochemistry, 2006, Vol 96, Issue 5, p1423
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2006.03648.x