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Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration

Nature Medicine volume 10, pages S26–S33 (2004)Cite this article

Abstract

Neurodegenerative diseases can be genetic or sporadic in origin. Genetic analysis has changed the study of the pathogenesis of these disorders by showing the causative functions of rare mutations. Yet, in the most common age-associated neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, the causes of neurodegeneration remain to be clarified. The observations that presenilin modulates proteolysis and turnover of several signaling molecules have led to speculations that pathways that are important in development may contribute to neurodegeneration. In this article, the possibility that these presenilin-regulated molecules may contribute to neurodegeneration is reviewed.

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Figure 1: Schematic showing the multiple physiological functions of presenilin.
Figure 2: Schematic of the dimer model of presenilin (PS) at the core of the γ-secretase complex that cleaves various substrates, including Notch and APP.
Figure 3: Schematic showing the type I membrane proteins that are known substrates for γ-secretase and presenilin.

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Acknowledgements

The authors thank S. Colamarino for reviewing the manuscript and for her suggestions, and M. Mehler for previous discussions. Studies from the authors' laboratories have been supported in part by grants NIH GM 55479 (R.K.), NS 28121 (E.H.K.), AG05131 (E.H.K.), Alzheimer's Association Grant RG991516 (R.K.) and Zenith Award ZEN-01-3050 (R.K.).

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  1. Department of Neurosciences, University of California, San Diego, La Jolla, 92093, California

    Edward H Koo

  2. Departments of Molecular Biology and Pharmacology and Medicine, Washington University School of Medicine, St. Louis, 63110, Missouri

    Raphael Kopan

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Correspondence to Edward H Koo.

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Koo, E., Kopan, R. Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration. Nat Med 10 (Suppl 7), S26–S33 (2004). https://doi.org/10.1038/nm1065

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