Deficiency of the Mre11 DNA repair complex in Alzheimer's disease brains.
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.
Jacobsen
Elizabeth
E
Molecular and Cellular Biology Program, School of Life Science, Arizona Biodesign Institute, Arizona State University, Tempe, AZ 85287-4501, USA.
Beach
Thomas
T
Shen
Yong
Y
Li
Rena
R
Chang
Yung
Y
D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D000076228:MRE11 Homologue Protein; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D046911:Macromolecular Substances; C112156:NBN protein, human; D009687:Nuclear Proteins; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes