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Related Experiment Videos

Gamma-secretase: never more enigmatic.

S S Sisodia1, W Annaert, S H Kim

  • 1Center for Molecular Neurobiology, Dept of Neurobiology, Pharmacology and Physiology, The University of Chicago, IL 60637, USA. ssisodia@drugs.bsd.uchicago.edu

Trends in Neurosciences
|March 8, 2002
PubMed
Summary

Alzheimer's disease pathogenesis involves beta-amyloid (Aβ) deposition. This review questions the role of presenilins (PS) as the gamma-secretase enzyme responsible for Aβ production from amyloid precursor protein (APP).

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Alzheimer's disease (AD) pathogenesis is linked to beta-amyloid (Aβ) peptide deposition in the brain.
  • Aβ peptides are generated from amyloid precursor protein (APP) by beta- and gamma-secretase enzymes.
  • The identity of gamma-secretase remains elusive, despite significant research.

Purpose of the Study:

  • To review evidence implicating presenilins (PS) in APP processing.
  • To present arguments against the hypothesis that PS function as gamma-secretases.
  • To discuss the ongoing enigma of gamma-secretase identification.

Main Methods:

  • Literature review of existing studies on APP processing and secretase activity.
  • Analysis of evidence supporting and refuting the role of presenilins (PS) as gamma-secretases.

Related Experiment Videos

  • Synthesis of current understanding regarding intramembranous protein processing.

    • Main Results:

    • Accumulating evidence suggests presenilins (PS) may not be the primary gamma-secretases.
    • The precise molecular identity and function of gamma-secretase remain under investigation.
    • Alternative models for APP processing are being considered.

    Conclusions:

    • The prevailing hypothesis of PS functioning as gamma-secretases warrants critical re-evaluation.
    • Further research is crucial to definitively identify the gamma-secretase complex.
    • Understanding APP processing is key to developing effective Alzheimer's disease therapies.