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Impact of muscarinic agonists for successful therapy of Alzheimer’s disease

  • A. Fisher
  • R. Brandeis
  • R. Haring
  • N. Bar-Ner
  • M. Kliger-Spatz
  • N. Natan
  • H. Sonego
  • I. Marcovitch
  • Z. Pittel
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)

Abstract

The Ml muscarinic agonists AF102B, AF150(S) & AF267B — i) restored cognitive impairments in several animal models for AD with an excellent safety margin; ii) elevated α-APPs levels; iii) attenuated vicious cycles induced by Aβ, and inhibited Aβ-and oxidative stress-induced apoptosis; and iv) decreased τ hyperphosphorylation. AF150(S) and AF267B were more effectve than rivastigmine and nicotine in restoring memory impairments in mice with small hippocampi. In apolipoprotein E-knockout mice, AF150(S) restored cognitive impairments and cholinergic hypofunction and decreased τ hyperphosphorylation. In aged microcebes, AF150(S) restored cognitive and behavioral impairments and decreased τ hyperphosphorylation, paired helical filaments and astrogliosis. In rabbits, AF267B & AF150(S) decreased CSF Aβ(1–42 & 1–40), while AF102B reduced Aβ(1–40). Finally AF102B decreased CSF Aβ(total) in AD patients. Taken together, M1 agonists may represent a unique therapy in AD due to their beneficial effects on three major hallmarks of AD — cholinergic hypofunction, Aβ and τ protein hyperphosphorylation.

Keywords

Nerve Growth Factor Reactive Oxidative Species Muscarinic Agonist PC12M1 Cell Cholinergic Hypofunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • A. Fisher
    • 1
  • R. Brandeis
    • 1
  • R. Haring
    • 1
  • N. Bar-Ner
    • 1
  • M. Kliger-Spatz
    • 1
  • N. Natan
    • 1
  • H. Sonego
    • 1
  • I. Marcovitch
    • 1
  • Z. Pittel
    • 1
  1. 1.Israel Institute for Biological ResearchNess-Ziona

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