AlzSWAN Knowledge Base

Powered by SWAN (Semantic Web Applications in Neuromedicine)

• Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins.
• Citation:
  Wang X, Su B, Siedlak S, Moreira P, Fujioka H, Wang Y, Casadesus G, Zhu X
  

  Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins.

  Proceedings of the National Academy of Sciences of the United States of America. 2008 Dec 9;105(49):19318-23
  [PubMed] [Alzforum]
• Supporting:
  • The events occurring at the dendritic spine remain to be resolved though likely involve mitochondrial alterations.

    SHOW Details   Supporting(3)   Alternative to: (4)

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

    • Wang X, Su B, Perry G, Smith M, Zhu X
      Insights into amyloid-beta-induced mitochondrial dysfunction in Alzheimer disease.
      Free radical biology & medicine. 2007 Dec 15;43(12):1569-73
    • Wang X, Su B, Siedlak S, Moreira P, Fujioka H, Wang Y, Casadesus G, Zhu X
      Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins.
      Proceedings of the National Academy of Sciences of the United States of America. 2008 Dec 9;105(49):19318-23
    • Wang X, Su B, Fujioka H, Zhu X
      Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients.
      The American journal of pathology. 2008 Aug;173(2):470-82

    Alternative statements
    

    • Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal Networks. Kuchibhotla K  Goldman S  Lattarulo C  Wu H  Hyman B  Bacskai B 
    • Amyloid-β protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory Shankar G  Li S  Mehta T  Garcia-Munoz A  Shepardson N  Smith I  Brett F  Farrell M  Rowan M  Lemere C  Regan C  Walsh D  Sabatini B  Selkoe D 
    • Increased dendritic excitability can increase Ca2+ influx, which can, in early stages, influence synaptic physiology and later lead to excitotoxic effects first within the dendrites, and later on, in the entire neuron. Morse T  Mutalik P  Cheung K  Miller P  Shepherd G 
    • The cognitive deficits of early Alzheimer Disease are caused by the disruption of electrical activity and information processing in dendrites of cortical pyramidal neurons. Morse T  Mutalik P  Cheung K  Miller P  Shepherd G 
  • A Short Circuit to Alzheimer Disease: Petersen et al Comment on Morse Hypothesis “The cognitive deficits of early Alzheimer Disease are caused by the disruption of electrical activity and information processing in dendrites of cortical pyramidal neurons.”
    Petersen R, Castellani R, Nunomura A, Zhu X, Lee H, Perry G, Smith M Mon, Apr 13 2009 15:07:22 EDT SHOW Details 
    The hypothesis proposed by Morse and colleagues that the cognitive deficits associated with Alzheimer disease result from the disruption of electrical activity provides a novel conceptual basis for understanding the clinical manifestation of the disease. A cogent discussion of the initial factors that may result in the electrical disturbance is unfortunately lost in the Morse hypothesis and merits discussion. The fleshing out of this interesting hypothesis may prove important for the development of novel therapeutic targets. Full text Comment (submitted online) from: Robert B. Petersen, Rudy J. Castellani, Akihiko Nunomura, Xiongwei Zhu, Hyoung-gon Lee, George Perry, Mark A. Smith The hypothesis by Morse and colleagues that the cognitive deficits associated with Alzheimer disease result from the disruption of electrical activity provides a novel conceptual basis for understanding the clinical manifestation of the disease. Whereas a significant emphasis has been placed on categorizing the various molecules implicated in the disease, relatively little attention has been paid to the underlying deficits that create the disease phenotype; memory deficit. Specific insights that bear examining are the apparent disconnect between the end-stage pathology, i.e., plaques and tangles, and the severity of cognitive decline (Castellani et al. 2006). A cogent discussion of the initial factors that may result in the electrical disturbance is unfortunately lost in the hypothesis and merits discussion. While amyloid-β (Aβ) may play a downstream role through perturbation of Ca2+ homeostasis, oxidative stress as the initiator needs to be addressed since oxidative stress affects both Aβ production and tau phosphorylation (Perez et al. 2000; Gomez-Ramos et al. 2003; Dozza et al. 2004; Tamagno et al. 2005; Tamagno et al. 2008; Guglielmotto et al. 2009). In contrast, the early role for oxidative damage preceding Aβ accumulation has been extensively documented in Alzheimer disease (Nunomura et al. 2001), Down syndrome (Nunomura et al. 2000), and in transgenic models (Pratico et al. 2001). Further, a direct interaction between Aβ and the A-type K+ channel has not been demonstrated. That said, mediation of the Aβ effect through the cellular prion protein has recently been proposed (Lauren et al. 2009); in prion null animals blockade of LTP by Aβ is absent. The events occurring at the dendritic spine remain to be resolved though likely involve mitochondrial alterations (Wang et al. 2008; Wang et al. 2008). In sum, the fleshing out of this interesting hypothesis may prove important for the development of novel therapeutic targets.
    

    • Tamagno et al., 2008
    • Laurén et al., 2009
    • Gómez-Ramos et al., 2003
    • Castellani et al., 2006
    • Pérez et al., 2000
    • Nunomura et al., 2001
    • Praticò et al., 2001
    • Dozza et al., 2004
    • Tamagno et al., 2005
    • Wang et al., 2008
    • Giliberto et al., 2009
    • Nunomura et al., 2000
    • Wang et al., 2008
• Created On: Mon, Mar 23 14:23:07 EDT 2009
• Last Modified On: Mon Mar 23 14:23:07 EDT 2009