Increased lnterleukin-1β Converting Enzyme Expression and Activity in Alzheimer Disease
| Autor: | Robert E. Mrak, S. G. Zhu, R. A. Jones, X. Q. Zhou, W. S. T. Griffin, J. G. Sheng, M. M. Brewer |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Pathology DNA damage Blotting Western Caspase 1 Hippocampus Biology Pathology and Forensic Medicine Cellular and Molecular Neuroscience Alzheimer Disease Internal medicine In Situ Nick-End Labeling medicine Humans RNA Messenger Senile plaques Neurodegeneration Brain Interleukin General Medicine medicine.disease Cortex (botany) Endocrinology Neurology Case-Control Studies Female Neurology (clinical) Alzheimer's disease DNA Damage |
| Zdroj: | Journal of Neuropathology and Experimental Neurology. 58:582-587 |
| ISSN: | 0022-3069 |
| DOI: | 10.1097/00005072-199906000-00002 |
| Popis: | Increased expression of interleukin-1 in Alzheimer disease (AD) has been implicated as a driving force in neurodegenerative cascades that underlie the formation of neuritic plaques and neurofibrillary tangles, the spread of these neuropathological lesions across cerebral cortical regions, and the accompanying neuronal cell injury and loss. The beta isoform of interleukin-1 is generated from an inactive, 33-kDa precursor through the action of a specific interleukin-1beta converting enzyme (ICE), also known as caspase-1. We used mesial temporal tissue (hippocampus and parahippocampal cortex) obtained postmortem from Alzheimer and control patients for determinations of endogenous tissue ICE activity and for Western immunoblot analysis of tissue ICE concentrations. ICE activity in Alzheimer tissue was elevated 50-100% (p < 0.002, or better, at incubation times of 30 min to 10 h), and ICE protein level was elevated 180% (p = 0.01). Parahippocampal cortex of Alzheimer patients showed increased numbers of neurons with in situ evidence of DNA damage. Increased DNA degradation was also evident upon electrophoresis of isolated DNA. Overexpression and increased activity of ICE may contribute to neurodegeneration in AD through generation of biologically active interleukin-1, with consequent activation of interleukin-1-driven neurodegenerative cascades. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|