Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration

Nat Med. 2004 Jul;10 Suppl:S26-33. doi: 10.1038/nm1065.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspases / metabolism
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Models, Neurological
  • Nerve Degeneration / physiopathology*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology*
  • Presenilin-1
  • Presenilin-2
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Notch
  • Signal Transduction / physiology*
  • Wnt Proteins


  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2
  • Proto-Oncogene Proteins
  • Receptors, Notch
  • Wnt Proteins
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Caspases