Chapter 49. Presenilins and Notch Signaling Pathway

  1. Khalid Iqbal3,
  2. Sangram S. Sisodia4,
  3. Bengt Winblad5
  1. Weihong Song*,
  2. Bruce A. Yankner*

Published Online: 18 APR 2002

DOI: 10.1002/0470846453.ch49

Book Title

Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics

Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics

Additional Information

How to Cite

Song, W. and Yankner, B. A. (2002) Presenilins and Notch Signaling Pathway, in Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics (eds K. Iqbal, S. S. Sisodia and B. Winblad), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470846453.ch49

Editor Information

  1. 3

    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314-6399, USA

  2. 4

    Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Abbot 316, 947 East 58th Street, Chicago, IL 60637, USA

  3. 5

    Karolinska Institute, NEUROTEC, Huddinge University Hospital, B 84, S-141 86 Huddinge, Stockholm, Sweden

Author Information

  1. Department of Neurology, The Children's Hospital, Harvard Medical School, Enders 260, 300 Longwood Avenue, Boston, MA 02115, USA

*Department of Neurology, The Children's Hospital, Harvard Medical School, Enders 260, 300 Longwood Avenue, Boston, MA 02115, USA Tel: +1 617 355 7087; fax: +1 617 738 1542;

Publication History

  1. Published Online: 18 APR 2002
  2. Published Print: 28 MAR 2001

ISBN Information

Print ISBN: 9780471521761

Online ISBN: 9780470846452

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Keywords:

  • Alzheimer's disease;
  • dementia;
  • presenilins;
  • notch signalling;
  • amyloid-β

Summary

Notch-1 is a member of a conserved family of transmembrane receptors that regulate cell fate decisions during development. A role for presenilins in the regulation of Notch signalling has been suggested by studies of the Caenorhabditis elegans presenilin homolog sel-12. These findings suggest that PS1 may regulate the Notch signaling pathway during development, although the cellular mechanism is unknown. We explore the possibility that PS1 and PS2 may also regulate proteolytic cleavage of Notch-1 intracellular domain. We now report that presenilins are absolutely required for the proteolytic release and nuclear translocation of the Notch-1 intracellular domain.

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