Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains

Elizabeth Jacobsen, Thomas Beach, Yong Shen, Rena Li, Yung Chang

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The hallmarks of Alzheimer's disease (AD) brains are deposition of Abeta plaques, appearance of neurofibrillary tangles, and extensive loss of neuronal cells. While Abeta plaques and neurofibrillary tangles play a significant role in the pathogenic dysfunction of neurons, factors that accelerate the neurodegenerating process remain to be defined. One set of factors examined in this study is the Mre11 protein complex, composed of Rad50, Mre11 and Nbs1. This protein complex plays an essential role in cellular responses to DNA damage, such as initiating cell cycle checkpoints and repairing damaged DNA. A defect in any component of this protein complex is detrimental to cells. Recently, several groups have observed abnormal cell cycle regulation and/or accumulated DNA damage in AD neurons. These pathological alterations could conceivably be caused or exacerbated by any compromise in the Mre11 complex. In this study, we compared the levels of the Mre11 complex proteins in brain samples from AD and age-matched non-dementia controls. We show for the first time that the Mre11 complex proteins are present in neurons of the adult human cortex and cerebellum. These proteins were found substantially reduced in the neurons of AD cortex. Our finding suggests that the loss of the Mre11 complex may be associated with the pathogenesis of AD.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalMolecular Brain Research
Volume128
Issue number1
DOIs
StatePublished - Sep 10 2004

Fingerprint

DNA Repair-Deficiency Disorders
Alzheimer Disease
Brain
Neurons
Neurofibrillary Tangles
Proteins
DNA Damage
Cell Cycle Checkpoints
Cerebellum
Cell Cycle
DNA

Keywords

  • Cell cycle checkpoint
  • DNA damage recognition and repair
  • Genome instability
  • Mre11 protein complex
  • Neurodegeneration
  • Post-mitotic neurons

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains. / Jacobsen, Elizabeth; Beach, Thomas; Shen, Yong; Li, Rena; Chang, Yung.

In: Molecular Brain Research, Vol. 128, No. 1, 10.09.2004, p. 1-7.

Research output: Contribution to journalArticle

Jacobsen, Elizabeth ; Beach, Thomas ; Shen, Yong ; Li, Rena ; Chang, Yung. / Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains. In: Molecular Brain Research. 2004 ; Vol. 128, No. 1. pp. 1-7.
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