ArticleThe American journal of pathology2005
Characterization of cell death pathways in human immunodeficiency virus-associated encephalitis.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
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- Syncytial apoptosis signaling network induced by the HIV-1 envelope glycoprotein complex: an overview.Cell death & disease · 2015Review
- p53 as a retrovirus-induced oxidative stress modulator.The Journal of general virology · 2015Article
- Autophagy plays an important role in the containment of HIV-1 in nonprogressor-infected patients.Autophagy · 2014Article
- Role of p53 in neurodegenerative diseases.Neuro-degenerative diseases · 2012Review
- Frontier of epilepsy research - mTOR signaling pathway.Experimental & molecular medicine · 2011Review
- The tumor suppressor protein PML controls apoptosis induced by the HIV-1 envelope.Cell death and differentiation · 2009Article
- PUMA, a potent killer with or without p53.Oncogene · 2008Review
- Avoiding the void: cell-to-cell spread of human viruses.Nature reviews. Microbiology · 2008Review
- Critical involvement of the ATM-dependent DNA damage response in the apoptotic demise of HIV-1-elicited syncytia.PloS one · 2008Article
- The glial response to CNS HIV infection includes p53 activation and increased expression of p53 target genes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2007Article
- Role of the transcription factor E2F1 in CXCR4-mediated neurotoxicity and HIV neuropathology.Neurobiology of disease · 2007Article
- Current development of mTOR inhibitors as anticancer agents.Nature reviews. Drug discovery · 2006Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus (HIV)-associated dementia is a neurodegenerative syndrome characterized by cognitive decline, personality change, and motor deficits. HIV-associated encephalitis (HAE), the neuropathology responsible for HIV-associated dementia, involves the formation of multinucleated giant cells or syncytia. In this article we describe the apoptotic pathways activated in the brains of HAE-affected patients. Approximately 50% of multinuclear giant cells exhibited apoptotic DNA fragmentation as detected by the terminal dUTP nick-end labeling technique. In addition, the presence of syncytia in the frontal cortex of approximately 35% of HAE patients correlated with the number of cells expressing the HIV-1 protein p24. Histochemical and immunohistochemical analyses revealed that HAE-associated syncytia underwent apoptosis through a mitochondrial pathway previously delineated for HIV-1 envelope-elicited syncytia in vitro. We observed over-expression of the mammalian target of rapamycin (mTOR), a kinase that mediates activation of the pro-apoptotic transcription factor p53, and p53-dependent up-regulation of two effectors of mitochondrial apoptosis, namely the BH3-only proteins Puma and transglutaminase type 2 (TG2). Interestingly, although mTOR activation and Puma induction were observed in dying syncytia and neurons, IkB phosphorylation and TG2 up-regulation were only found in syncytia. These findings provide substantial new information on the cell death mechanisms that regulate HAE, suggesting an important pathogenetic role of syncytia in the disease.
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