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• Genetic dissection of gamma-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death.
• Citation:
  Kallhoff-Munoz V, Hu L, Chen X, Pautler R, Zheng H
  

  Genetic dissection of gamma-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death.

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008 Oct 29;28(44):11421-31
  [PubMed] [Alzforum]
• Supporting:
  • Neurons that show Aβ accumulations may attempt to reenter the cell cycle.

    SHOW Details   Supporting(3)   Consistent(5)   Inconsistent(1)   Alternative to: (1)

    Description: CAD cells that show the Aβ accumulations clearly have something in common. One possibility is that the neuritic Aβ phenotype could result from a failed attempt of neurons to re-enter the cell cycle. Recent work indicates that in AD brains, as well as in mouse models of AD, ectopic initiation of cell-cycle processes in neurons is an early sign of neuronal distress and increased vulnerability to insults. Although Aβ accumulating cells are only found in cultures maintained under differentiating conditions, they are in fact detectable very early after switching to differentiating conditions, when some cells may still attempt to undergo mitosis. This possibility remains to be tested.
    Experimental Approach: Pathophysiology,   Mechanism - molecular and cell
    Pathogenic Narrative Tags: Pathogenic event
    Supporting Evidence
    

    • Yang Y, Varvel N, Lamb B, Herrup K
      Ectopic cell cycle events link human Alzheimer's disease and amyloid precursor protein transgenic mouse models.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006 Jan 18;26(3):775-84
    • Kallhoff-Munoz V, Hu L, Chen X, Pautler R, Zheng H
      Genetic dissection of gamma-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008 Oct 29;28(44):11421-31
    • Varvel N, Bhaskar K, Patil A, Pimplikar S, Herrup K, Lamb B
      Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease.
      The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008 Oct 22;28(43):10786-93

    Consistent statements
    

    • It is possible that LC neurons that show CCEs have their projections in the hippocampus and cortex, where plaques are regularly found. Muresan Z  Muresan V 
    • Aβ oligomers induce neuronal cell cycle events in Alzheimer disease. Varvel N  Bhaskar K  Patil A  Pimplikar S  Herrup K  Lamb B 
    • Inappropriate reactivation of the cell cycle is an early and important event in the development of Alzheimer disease. Vincent I  Rosado M  Davies P 
    • Neurons that show CCE do not retract their processes before doing so. Muresan Z  Muresan V 
    • Several reports describe aberrant regulation of cell cycle factors in AD brain. Suzuki T 

    Inconsistent statements
    

    • Neuronal cell cycle events (CCEs) are also observed in the locus ceruleus and dorsal raphe at 8 months in the R1.40 mice, two brain regions in which no Aβ deposition is observed even at late ages. Varvel N  Bhaskar K  Patil A  Pimplikar S  Herrup K  Lamb B 

    Alternative statements
    

    • Cortical cell cycle events (CCEs) appear ~8 months before the onset of fibrillar Aβ deposition in the B6- R1.40 model suggesting that fibrillar Aβ deposits are not responsible for the induction of neuronal CCEs and instead implicates either unique soluble Aβ species or particular APP processing products. Varvel N  Bhaskar K  Patil A  Pimplikar S  Herrup K  Lamb B 
• Created On: Tue, Dec 02 09:09:10 EST 2008
• Last Modified On: Tue Dec 02 09:09:10 EST 2008