Articles - Neurobiology of Disease: Neuroprotective Effects of Regulators of the Glycogen Synthase Kinase-3β Signaling Pathway in a Transgenic Model of Alzheimer's Disease Are Associated with Reduced Amyloid Precursor Protein Phosphorylation
  • Edward Rockenstein,
  • Magdalena Torrance,
  • Anthony Adame,
  • Michael Mante,
  • Pazit Bar-on,
  • John B. Rose,
  • Leslie Crews,
  • and Eliezer Masliah
The Journal of Neuroscience, 21 February 2007, 27(8):1981-1991; doi:10.1523/JNEUROSCI.4321-06.2007

  1. GSK in Alzheimer's disease

    Loyola University Chicago Stritch School of Medicine, Edward Hines, Jr. Veterans Affairs Hospital, H

    It was quite gratifying to read the elegant report of Rockenstein et al. showing the protective effects of decreasing levels of activated GSK3beta, which were associated with improved behavioral performance and decreased tau phosphorylation in transgenic mice. These results bear out our earlier results (not cited in this paper) that decreased levels of activated GSK3beta induced by propentophylline were associated with decreased tau phosphorylation (1) and, in separate experiments, that propentophylline also induced decreased Abeta levels in transgenic mice (2), thus suggesting the plausible hypothesis that GSK3beta may be the link between amyloid and hyperphosphorylated tau in Alzheimer's disease (1, 3). The results reported by Rockenstein et al. provide additional evidence consistent with this hypothesis. In view of the mounting evidence, it would be important to attempt to prove or disprove this hypothesis. Two interesting experiments would be (1) to test whether lithium or propentophylline would reduce activated GSK3b and block hyperphosphorylation of tau in mice harboring mutant human tau genes related to tauopathies and (2) whether the mutant tau gene would lead to hyperphosphorylated tau in GSK-null mice.

    1. Chauhan NB, Siegel GJ, Feinstein DL, Propentophylline attenuates tau phosphorylation in Alzheimer's Swedish mutant model Tg2576, Neuropharmacology, 2005, 48:93-104.

    2. Chauhan NB and Siegel GJ, Effect of PPF and ALCAR on the induction of NGF- and p75-mRNA and on APP processing in Tg2576 brain, Neurochem Int, 2003, 43:225-33.

    3. Siegel GJ, Chauhan NB and Karczmar AG, Links Between Amyloid and Tau Biology in Alzheimer's Disease and their Cholinergic Aspects, in [AG Karczmar, editor] Exploring the Vertebrate Central Cholinergic Nervous System, Springer Science+Busines Media LLC, 2007, pp 597-656.

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    Published November 12, 2008
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