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Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome

  • R. Seidl
  • M. Bajo
  • K. Böhm
  • E. C. LaCasse
  • A. E. MacKenzie
  • N. Cairns
  • G. Lubec
Conference paper

Summary

In Down syndrome (DS), enhanced apoptosis (programmed cell death) may play a role in the pathogenesis of characteristic early mental retardation and precocious neurodegeneration of Alzheimer-type.

The human IAP (inhibitor of apoptosis proteins) genes (NAIP, c-IAP-2/ HIAP-1, c-IAP-l/Hiap-2, XIAP, survivin) are an evolutionary conserved family of proteins which prevent cell death across species, implying that they act at a central, highly conserved point in the cell death cascade. Evidence for downregulation of NAIP-mRNA in fetal DS (23rd week of gestation), as found by subtractive hybridization technique challenged studies at the protein level in adult DS brain specimen.

NAIP-like immunoreactivity was determined in four different regions of cerebral cortex and cerebellum in 9 adult DS patients with Alzheimer-like neuropathologic lesions, 9 Alzheimer disease (AD) patients as compared to 9 controls. For the first time, NAIP-IR could be demonstrated in different cortical regions of the human brain. Compared to control subjects, western blotting demonstrated significantly decreased levels in parietal and occipital cortex in DS and in frontal and occipital cortex in AD. While the mode of NAIP action is unknown, inhibition of certain caspases has already been demonstrated for other IAP-family members (c-IAP1, C-IAP2 and XIAP). Although decreased NAIP-IR of certain brain regions in DS and AD awaits further confirmation, the results suggest that alterations of apoptosis regulatory (inhibitory) proteins may be another feature of neurodegeneration in DS and AD.

Keywords

Alzheimer Disease Down Syndrome Spinal Muscular Atrophy Cerebellar Granule Neuron Alzheimer Disease Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • R. Seidl
    • 1
  • M. Bajo
    • 2
  • K. Böhm
    • 1
  • E. C. LaCasse
    • 3
  • A. E. MacKenzie
    • 3
  • N. Cairns
    • 4
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Institute of NeuroimmunologySASBratislavaSlovakia
  3. 3.CHEO Research InstituteApoptogen Inc.OttawaCanada
  4. 4.Brain Bank, Institute of PsychiatryUniversity of LondonLondonUK

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