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• Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention.
• Citation:
  Zhao L, Teter B, Morihara T, Lim G, Ambegaokar S, Ubeda O, Frautschy S, Cole G
  

  Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention.

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 Dec 8;24(49):11120-6
  [PubMed] [Alzforum]
• Supporting:
  • Insulin increases the expression of the Aβ-protease, insulin degrading enzyme (IDE) and enhances the secretion of sAPPα, which results from the non-amyloidogenic α-secretase- mediated cleavage of APP.

    SHOW Details   Supporting(2)   Consistent(1)     Genes/Proteins: (2)

    Experimental Approach: Mechanism - biochemistry and structural biology,   Mechanism - molecular and cell
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Solano D, Sironi M, Bonfini C, Solerte S, Govoni S, Racchi M
      Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway.
      The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2000 May;14(7):1015-22
    • Zhao L, Teter B, Morihara T, Lim G, Ambegaokar S, Ubeda O, Frautschy S, Cole G
      Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 Dec 8;24(49):11120-6

    Consistent statements
    

    • Insulin and Aβ may exert reciprocal effects because insulin regulates Aβ levels by promoting its intracellular release from neurons, and regulates degradation and clearance of Aβ by insulin degrading enzyme (IDE); while Aβ impairs insulin signaling. Craft S 

    Genes/Proteins
    

    • Protein: Insulin [Homo sapiens]
    • Protein: Insulin-degrading enzyme [Homo sapiens]
  • Insulin and Aβ may exert reciprocal effects because insulin regulates Aβ levels by promoting its intracellular release from neurons, and regulates degradation and clearance of Aβ by insulin degrading enzyme (IDE); while Aβ impairs insulin signaling.

    SHOW Details   Supporting(5)   Consistent(2)   Alternative to: (1)    Genes/Proteins: (6)

    Experimental Approach: Mechanism - molecular and cell,   Mechanism - biochemistry and structural biology,   Mechanism - physiological systems,  
    Pathogenic Narrative Tags: Initial condition
    Supporting Evidence
    

    • Mukherjee R, Hoener P, Jow L, Bilakovics J, Klausing K, Mais D, Faulkner A, Croston G, Paterniti J
      A selective peroxisome proliferator-activated receptor-gamma (PPARgamma) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes.
      Molecular endocrinology (Baltimore, Md.). 2000 Sep;14(9):1425-33
    • Vekrellis K, Ye Z, Qiu W, Walsh D, Hartley D, Chesneau V, Rosner M, Selkoe D
      Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2000 Mar 1;20(5):1657-65
    • Zhao Z, Ho L, Wang J, Qin W, Festa E, Mobbs C, Hof P, Rocher A, Masur S, Haroutunian V, Pasinetti G
      Connective tissue growth factor (CTGF) expression in the brain is a downstream effector of insulin resistance- associated promotion of Alzheimer's disease beta-amyloid neuropathology.
      The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2005 Dec;19(14):2081-2
    • Gasparini L, Gouras G, Wang R, Gross R, Beal M, Greengard P, Xu H
      Stimulation of beta-amyloid precursor protein trafficking by insulin reduces intraneuronal beta-amyloid and requires mitogen-activated protein kinase signaling.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001 Apr 15;21(8):2561-70
    • Zhao L, Teter B, Morihara T, Lim G, Ambegaokar S, Ubeda O, Frautschy S, Cole G
      Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004 Dec 8;24(49):11120-6

    Consistent statements
    

    • Insulin increases the expression of the Aβ-protease, insulin degrading enzyme (IDE) and enhances the secretion of sAPPα, which results from the non-amyloidogenic α-secretase- mediated cleavage of APP. Hooper C  Killick R  Lovestone S 
    • Even moderate increases in IDE activity can lead to dramatic changes in steady-state Aβ levels as well as overall amyloid plaque burden. Tanzi R  Moir R  Wagner S 

    Alternative statements
    

    • Active site substrates for IDE can activate the enzyme toward hydrolyzing Aβ, but not insulin. Tanzi R  Moir R  Wagner S 

    Genes/Proteins
    

    • Protein: Insulin-degrading enzyme [Rattus norvegicus]
    • Protein: Beta-amyloid protein 42 [Homo sapiens]
    • Protein: Insulin [Homo sapiens]
    • Protein: Beta-amyloid protein 40 [Homo sapiens]
    • Protein: Insulin-degrading enzyme [Mus musculus]
    • Protein: Insulin-degrading enzyme [Homo sapiens]
• Created On: Sun, Nov 22 15:19:48 EST 2009
• Last Modified On: Sun Nov 22 15:19:48 EST 2009