Towards Alzheimer's root cause: ECSIT as an integrating hub between oxidative stress, inflammation and mitochondrial dysfunction. Hypothetical role of the adapter protein ECSIT in familial and sporadic Alzheimer's disease pathogenesis

Bioessays. 2012 Jul;34(7):532-41. doi: 10.1002/bies.201100193. Epub 2012 Apr 19.


Here we postulate that the adapter protein evolutionarily conserved signalling intermediate in Toll pathway (ECSIT) might act as a molecular sensor in the pathogenesis of Alzheimer's disease (AD). Based on the analysis of our AD-associated protein interaction network, ECSIT emerges as an integrating signalling hub that ascertains cell homeostasis by the specific activation of protective molecular mechanisms in response to signals of amyloid-beta or oxidative damage. This converges into a complex cascade of patho-physiological processes. A failure to repair would generate severe mitochondrial damage and ultimately activate pro-apoptotic mechanisms, promoting synaptic dysfunction and neuronal death. Further support for our hypothesis is provided by increasing evidence of mitochondrial dysfunction in the disease etiology. Our model integrates seemingly controversial hypotheses for familial and sporadic forms of AD and envisions ECSIT as a biomarker to guide future therapies to halt or prevent AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Age of Onset
  • Alzheimer Disease / genetics
  • Alzheimer Disease / immunology
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Apoptosis
  • Chromosomes, Human / genetics
  • Chromosomes, Human / metabolism
  • Genetic Predisposition to Disease
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Inflammation / immunology
  • Inflammation / pathology
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Mitochondria / pathology*
  • Oxidative Stress*
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Presenilin-2 / genetics
  • Presenilin-2 / metabolism
  • Protein Interaction Mapping
  • Protein Interaction Maps
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Amyloid beta-Peptides
  • Ecsit protein, human
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2