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• Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function.
• Citation:
  Huang S, Mouri A, Kokubo H, Nakajima R, Suemoto T, Higuchi M, Staufenbiel M, Noda Y, Yamaguchi H, Nabeshima T, Saido T, Iwata N
  

  Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function.

  The Journal of biological chemistry. 2006 Jun 30;281(26):17941-51
  [PubMed] [Alzforum]
• Supporting:
  • Manipulation of NEP and IDE in animal models shows that increasing or decreasing their activity can alter Aβ accumulation inversely as well as change synaptic function and behavior.

    SHOW Details   Supporting(3)   Consistent(4)     Genes/Proteins: (3)

    Experimental Approach: Mechanism - molecular and cell,   Animal models,  
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Madani R, Poirier R, Wolfer D, Welzl H, Groscurth P, Lipp H, Lu B, El Mouedden M, Mercken M, Nitsch R, Mohajeri M
      Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo.
      Journal of neuroscience research. 2006 Dec;84(8):1871-8
    • Huang S, Mouri A, Kokubo H, Nakajima R, Suemoto T, Higuchi M, Staufenbiel M, Noda Y, Yamaguchi H, Nabeshima T, Saido T, Iwata N
      Neprilysin-sensitive synapse-associated amyloid-beta peptide oligomers impair neuronal plasticity and cognitive function.
      The Journal of biological chemistry. 2006 Jun 30;281(26):17941-51
    • Eckman E, Eckman C
      Abeta-degrading enzymes: modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention.
      Biochemical Society transactions. 2005 Nov;33(Pt 5):1101-5

    Consistent statements
    

    • The life-long accumulation of Aβ in the brain is determined by the rate of Aβ generation versus clearance. Tanzi R  Moir R  Wagner S 
    • Primary neuronal cultures derived from IDE knockout mice are less effective at degrading radiolabeled Aβ, in vitro. Tanzi R  Moir R  Wagner S 
    • Aβ could be removed from the CNS or at peripheral degradation sites by enhancing the activity of the major degradation enzymes IDE and NEP. Tanzi R  Moir R  Wagner S 
    • Support for the role of IDE in AD pathogenesis stems from recent reports of its genetic association with late-onset AD. Tanzi R  Moir R  Wagner S 

    Genes/Proteins
    

    • Protein: Neprilysin [Mus musculus]
    • Gene: Mme membrane metallo endopeptidase [Mus musculus]
    • Gene: Ide insulin degrading enzyme [Mus musculus]
• Created On: Wed, Jun 11 12:56:29 EDT 2008
• Last Modified On: Wed Jun 11 12:56:29 EDT 2008