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Reduced IGF-1 signaling delays age-associated proteotoxicity in mice

Academic Article
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Overview

authors

  • Cohen, E.
  • Paulsson, J. F.
  • Blinder, P.
  • Burstyn-Cohen, T.
  • Du, D. G.
  • Estepa, G.
  • Adame, A.
  • Pham, H. M.
  • Holzenberger, M.
  • Kelly, Jeffery
  • Masliah, E.
  • Dillin, A.

publication date

  • 2009

journal

  • Cell  Journal

abstract

  • The insulin/insulin growth factor (IGF) signaling (IIS) pathway is a key regulator of aging of worms, flies, mice, and likely humans. Delayed aging by IIS reduction protects the nematode C. elegans from toxicity associated with the aggregation of the Alzheimer's disease-linked human peptide, Abeta. We reduced IGF signaling in Alzheimer's model mice and discovered that these animals are protected from Alzheimer's-like disease symptoms, including reduced behavioral impairment, neuroinflammation, and neuronal loss. This protection is correlated with the hyperaggregation of Abeta leading to tightly packed, ordered plaques, suggesting that one aspect of the protection conferred by reduced IGF signaling is the sequestration of soluble Abeta oligomers into dense aggregates of lower toxicity. These findings indicate that the IGF signaling-regulated mechanism that protects from Abeta toxicity is conserved from worms to mammals and point to the modulation of this signaling pathway as a promising strategy for the development of Alzheimer's disease therapy.

subject areas

  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Animals
  • Humans
  • Insulin-Like Growth Factor I
  • Longevity
  • Male
  • Mice
  • Mice, Transgenic
  • Presenilin-1
  • Receptor, IGF Type 1
  • Signal Transduction
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Identity

PubMed Central ID

  • PMC3017511

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2009.11.014

PubMed ID

  • 20005808
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Additional Document Info

start page

  • 1157

end page

  • 1169

volume

  • 139

issue

  • 6

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