ArticleNeuropathology and applied neurobiology2012
Activation status of integrated stress response pathways in neurones and astrocytes of HIV-associated neurocognitive disorders (HAND) cortex.
Article in Neuropathology and applied neurobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 47 citations in OpenAlex.
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- Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
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- Update on Central Nervous System Effects of HIV in Adolescents and Young Adults.Current HIV/AIDS reports · 2023Review
- Human iPSC-derived neurons reveal NMDAR-independent dysfunction following HIV-associated insults.Frontiers in molecular neuroscience · 2023Article
- PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.Journal of neurology and psychology · 2023Article
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- Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults.PLoS genetics · 2021Article
- Protease Inhibitors, Saquinavir and Darunavir, Inhibit Oligodendrocyte Maturation: Implications for Lysosomal Stress.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
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- Cal'MAM'ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2021Review
- Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders.Journal of neurovirology · 2020Review
- Neuroinflammation and EIF2 Signaling Persist despite Antiretroviral Treatment in an hiPSC Tri-culture Model of HIV Infection.Stem cell reports · 2020Article
- The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration.Journal of neuropathology and experimental neurology · 2020Review
- Proteomic analysis of cerebrospinal fluid extracellular vesicles reveals synaptic injury, inflammation, and stress response markers in HIV patients with cognitive impairment.Journal of neuroinflammation · 2019Article
- White matter loss and oligodendrocyte dysfunction in HIV: A consequence of the infection, the antiretroviral therapy or both?Brain research · 2019Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsCombined 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.
methodsTo 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.
resultsThe 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.
conclusionThese findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.
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