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Related Experiment Videos

Gamma-secretase--intramembrane protease with a complex.

Michael S Wolfe1

  • 1Center for Neurologic Diseases at Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. mwolfe@rics.bwh.harvard.edu.

Science of Aging Knowledge Environment : SAGE KE
|July 8, 2003
PubMed
Summary

Gamma-secretase, an enzyme linked to Alzheimer's disease and embryonic development, is a complex of four proteins. Its presenilin component undergoes autocleavage to form the active site, revealing a novel class of proteases.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Gamma-secretase is implicated in Alzheimer's disease pathogenesis via amyloid beta protein precursor cleavage.
  • This protease also plays a critical role in embryonic development by cleaving the Notch receptor.

Purpose of the Study:

  • To elucidate the molecular composition and mechanism of gamma-secretase.
  • To understand the active site formation of this intramembrane-cleaving protease.

Main Methods:

  • Analysis of gamma-secretase complex composition.
  • Investigating presenilin autocleavage and its role in enzyme activity.

Main Results:

  • Gamma-secretase comprises at least four proteins: presenilin, nicastrin, Aph-1, and Pen-2.

Related Experiment Videos

  • Presenilin undergoes autocleavage into two subunits, forming the enzyme's active site.

    • Conclusions:

    • Gamma-secretase is a multi-protein complex with an unusual autocleavage mechanism for active site formation.
    • Understanding gamma-secretase is crucial for therapeutic strategies targeting Alzheimer's disease and for comprehending intramembrane proteolysis.