Important note: Information in this article was accurate in June 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; June 24, 2002
Michael Greer, Senior Medical Writer
"Cell cycle proteins regulate processes as diverse as cell division and cell death," explained Dr. Kelly L. Jordan-Sciutto and colleagues at the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania. "Recently their role in neuronal death has been reported in several models of neurodegeneration."
Levels of several key cell cycle proteins were elevated in patients suffering from HIVE, Jordan-Sciutto and coauthors found.
In previous studies, the researchers observed significantly heightened levels of the transcription factor E2F1 and the retinoblastoma susceptibility gene product (pRb) during encephalitis triggered by the simian version of HIV. Similar increases in E2F1 activity were seen in HIVE patients, who also showed elevated levels of the inactivated, hyperphosphorylated form of pRb (ppRb), they said.
Heightened E2F1 and ppRb levels were accompanied by increased numbers of activated macrophages migrating to the affected areas, study data showed. The rise in macrophage activity could contribute to neurodegenerative inflammation.
Patients with HIVE also showed elevated activity from E2F/DNA binding complexes in the basal ganglia and midfrontal cortex (Cell cycle proteins exhibit altered expression patterns in lentiviral-associated encephalitis, J Neurosci 2002 Mar 15;22(6):2185-95.
"These findings suggest that changes in cell cycle proteins occur in both HIVE and the simian model," Jordan-Sciutto and colleagues concluded, "and that these changes have functional implications for gene expression in neural cells under encephalitic conditions mediated by macrophage activation or infiltration."
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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