About: Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex

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About: Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex Goto Sponge NotDistinct Permalink

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex
Creator	Wang, Y Akay, C Goenaga-Vazquez, Y Jordan-Sciutto, K Kolson, D Lindl, K Nabet, B Ruzbarsky, J Shyam, N Jordan, K
Source	Medline; PMC
abstract	AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/ microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. METHODS: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. CONCLUSION: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.
has issue date	2012-03-05(xsd:dateTime)
bibo:doi	10.1111/j.1365-2990.2011.01215.x
bibo:pmid	21883374
has license	green-oa
sha1sum (hex)	82daedbf36cc44af6d0076c5adf37c2de33f2360
schema:url	https://doi.org/10.1111/j.1365-2990.2011.01215.x
resource representing a document's title	Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex
has PubMed Central identifier	PMC3708539
has PubMed identifier	21883374
schema:publication	Neuropathology and Applied Neurobiology
resource representing a document's body	covid:82daedbf36cc44af6d0076c5adf37c2de33f2360#body_text
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